Home / Deep Research / 2q37 Microdeletion Syndrome

2q37 Microdeletion Syndrome

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of 2q37 Microdeletion Syndrome. Core disease mechanisms, molecular and cellul...

2026-04-15
Asta MONDO:0010886 Model: Asta Scientific Corpus Retrieval 19 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of 2q37 Microdeletion Syndrome. Core disease mechanisms, molecular and cellul...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 19
  • Snippets retrieved: 20

Relevant Papers

[1] A Rare Case of Concurrent 2q34q36 Duplication and 2q37 Deletion in a Neonate with Syndromic Features

  • Authors: F. N. Riviello, Alessia Daponte, Emanuela Ponzi, R. Ficarella, Paola Orsini et al.
  • Year: 2023
  • Venue: Genes
  • URL: https://www.semanticscholar.org/paper/c3e3702d27e0e18be3de627ebca4ca14e443936c
  • DOI: 10.3390/genes14122194
  • PMID: 38137016
  • PMCID: 10742419
  • Citations: 1
  • Summary: An extensive molecular analysis of a 15-day-old newborn referred for syndromic features reveals an 8.5 Mb microdeletion at 2q37.1, which extends to the telomere, in conjunction with an 8.6 Mb interstitial microduplication at 2q34q36.1.
  • Evidence snippets:
  • Snippet 1 (score: 0.590) > Large-scale genomic structural variations can have significant clinical implications, depending on the specific altered genomic region. Briefly, 2q37 microdeletion syndrome is a prevalent subtelomeric deletion disorder characterized by variable-sized deletions. Affected patients exhibit a wide range of clinical manifestations, including short stature, facial dysmorphism, and features of autism spectrum disorder, among others. Conversely, isolated duplications of proximal chromosome 2q are rare and lack a distinct phenotype. In this report, we provide an extensive molecular analysis of a 15-day-old newborn referred for syndromic features. Our analysis reveals an 8.5 Mb microdeletion at 2q37.1, which extends to the telomere, in conjunction with an 8.6 Mb interstitial microduplication at 2q34q36.1. Our findings underscore the prominence of 2q37 terminal deletions as commonly reported genomic anomalies. We compare our patient’s phenotype with previously reported cases in the literature to contribute to a more refined classification of 2q37 microdeletion syndrome and assess the potential impact of 2q34q36.1 microduplication. We also investigate multiple hypotheses to clarify the genetic mechanisms responsible for the observed genomic rearrangement.
  • Snippet 2 (score: 0.531) > Structural chromosomal rearrangements involving large regions of one-to severalmegabase pairs arise through a variety of mechanisms often associated with particular features of genomic architecture, which can trigger genetic instability [1]. Chromosome abnormalities can have significant implications, particularly when they affect the balance of genes that can lead to the development of various diseases. > Chromosome imbalances affecting the long arm of chromosome 2 result in a variety of distinct clinical conditions. For example, 2q37 microdeletion syndrome, alternatively known as Albright hereditary osteodystrophy-like syndrome or brachydactyly-intellectual disability syndrome, is a rare genetic disorder resulting from a variable-sized deletion in the long (q) arm of chromosome 2 [2][3][4]. The syndrome is characterized by a broad spectrum of clinical findings: the most common phenotypic features include mild to moderate developmental delay/intellectual disability (ID), brachymetaphalangy of digits 3-5 (brachydactyly type E), short stature, obesity, hypotonia in infancy, abnormal behavior with autism spectrum disorder, joint hypermobility, and scoliosis. Most individuals with 2q37 deletion syndrome have a typical dysmorphic face: broad or rounded facies; frontal bossing; midface hypoplasia; thin, arched eyebrows with deep-set eyes; upslanting palpebral fissures; prominent columella; and minor ear defects. In 20-30% of cases, visceral Genes 2023, 14, 2194 2 of 10 malformations are also present: congenital heart disease (mostly septal defects), gastrointestinal or genitourinary anomalies, central nervous system malformations, renal anomalies, and Wilms tumors. Rarely, patients may have associated seizures and hyperactivity with attention deficit disorder [3]. > On the other hand, duplications of proximal chromosome 2q are rare, and no specific associated syndrome has been identified. The majority of trisomy 2q cases arise from parental rearrangements, often accompanied by a deletion of another chromosomal segment, which hampers phenotypic delineation.

[2] 7p22.3 microdeletion: a case study of a patient with congenital heart defect, neurodevelopmental delay and epilepsy

  • Authors: L. Skvortsova, A. Perfilyeva, K. Bespalova, Y. Kuzovleva, Nailya Kabysheva et al.
  • Year: 2024
  • Venue: Orphanet Journal of Rare Diseases
  • URL: https://www.semanticscholar.org/paper/408a30b232114d5edfca1ebdf0bc63e4382f59bb
  • DOI: 10.1186/s13023-024-03321-8
  • PMID: 39152504
  • PMCID: 11330011
  • Citations: 2
  • Summary: Through detailed genetic analyses, the clinical description of the rare 7p22.3 microdeletion in a patient with congenital heart defect and neurological abnormalities - epilepsy, combined with moderate mental and motor developmental delay is improved, creating a basis for future genetic counseling and research into targeted therapies.
  • Evidence snippets:
  • Snippet 1 (score: 0.482) > Complex disease phenotypes affecting different organ systems are the result of an individual's complex genetic landscape. Analysis of the literature data shows that there is a certain variability of phenotypes even in Mendelian diseases. Symptoms may vary in the presence/absence and severity from patient to patient. These individual phenotypes are the most noticeable in microdeletion syndromes when multiple genes are affected. One of these syndromes is Williams syndrome, which is caused by a heterozygous deletion 7q11.23 [11,12]. There are specific symptoms and features with a high frequency of occurrence (core symptoms, > 90% of cases) and less specific features with a frequency of < 90% (Morris 2023). The last ones are highly variable from patient to patient. This emphasizes that microdeletion syndromes are not a uniform disease but a group of etiologically heterogeneous conditions whose pathophysiology reflect an individual genetic profile. The functional activity of affected proteins and their involvement in cellular processes as well as the presence of additional structural changes in single-copy genes modulate a pathological phenotype. > In the present case, the patient A had most of the symptoms typical for Williams syndrome and was referred for a genetic counseling (to be confirmed by genetic testing). CMA revealed the absence of the specific microdeletion in the long arm of chromosome 7 (7q11.23) but the presence of another microdeletion in the short arm of chromosome 7 (7p22.3). The identified deletion is less common than the Williams syndrome deletion and some cases have been published. Deletion 7p22.3 phenotype is associated with various clinical symptoms including neurodevelopmental delay, congenital skeletal and heart abnormalities, hypotonia, craniofacial dysmorphism and other less common features [3]. To date, epilepsy has not been reported for this 7p22.3 deletion but it was observed in a patient with a combination of 7p22.3-p22.1 deletion and 8q24.23-q24.3 duplication.

[3] Pathway-based classification of genetic diseases

  • Authors: I. Iourov, S. Vorsanova, Y. Yurov
  • Year: 2019
  • Venue: Molecular Cytogenetics
  • URL: https://www.semanticscholar.org/paper/27a727e2b33eb986916fbd2dcb42b02e082b914d
  • DOI: 10.1186/s13039-019-0418-4
  • PMID: 30766616
  • PMCID: 6362588
  • Citations: 38
  • Summary: This work proposes an extension to the common disease classification based on the underlying genetic defects, which focuses on disease-specific molecular pathways, and follows the tradition of using ancient Greek words and prefixes to create the terms for the pathway-based classification of genetic diseases.
  • Evidence snippets:
  • Snippet 1 (score: 0.442) > Since etiology comprises the multilateral evaluation of how a disease can be classified, defined, and discovered [14], current classification of genetic diseases appears to require an update. > Although (cyto)genomic analysis is the permanent starting point for uncovering the mechanism and etiology of a disease, an indication of gene amount and a speculation about possible genetic-environmental interaction is certainly not enough for the disease designation at the present stage of development in the fields of (cyto)genomics and molecular (systems) medicine. The knowledge of the nature of genetic defects alone poorly defines the etiology of a disease. More precisely, mechanisms of phenotypic outcomes and molecular/cellular pathways to disease remain obscure without a presentation of additional etiologic aspects. Particularly, addressing numerical and structural abnormalities of chromosomes using "gene-centric" concepts is usually confined to the determination of amount of affected genes. However, it is possible that a limited number of genes within the rearranged chromosomal region are intrinsically involved in the clinical outcome. CNV or mutations in different genes attributed to the same pathway may have clinical outcomes similar to chromosome rearrangements or vice versa [7,13,15]. For instance, our previous studies of mutation-negative cases of a monogenic disease (Rett syndrome) have shown that the disease can be caused by subchromosome rearrangements (microdeletions), as well [16]. Even though it is the same disease from a clinical point of view, one has to differ between "monogenic" and "chromosomal" Rett syndrome. Single gene mutations are able to produce chromosomal/genomic instability, which is the underlying cause of the clinical outcome [17,18]. Genome/chromosome instability syndromes (monogenic syndromes) usually exhibit severe manifestations inasmuch as numerous molecular and cellular pathways are altered due to a mutation in a regulatory gene. Thus, it is quite strange that diseases associated with a single pathway defect (e.g. single enzymatic defect) are attributed to the same category as diseases associated with an extensive cascade of abnormal molecular and cellular events.

[4] Profile of DHX37 gene defects in human genetic diseases: 46,XY disorders of sex development

  • Authors: Huifang Peng, Wenyuan Peng, Jiali Chen, Keyan Hu, Yingyu Zhang et al.
  • Year: 2025
  • Venue: Frontiers in Endocrinology
  • URL: https://www.semanticscholar.org/paper/ff11ed0f8a3776fc0ef16b1d0673cc0735fc84a2
  • DOI: 10.3389/fendo.2025.1507749
  • PMID: 40026690
  • PMCID: 11867910
  • Citations: 1
  • Summary: Although the molecular mechanism of DHX37 mutation related 46,XY DSD is unclear, ribosome synthesis, cell cycle regulation, and the NF-κB and Wnt pathways may be affected.
  • Evidence snippets:
  • Snippet 1 (score: 0.441) > The RNA helicase DHX37 gene is involved in ribosomal biological processes, and linked to human genetic diseases associated with 46,XY disorders of sex development (46,XY DSD) or neurodevelopment. Recently, relevant reports have primarily focused on 46,XY DSD. However, there is still a lack of overall understanding of the genetic characteristics, phenotype, etc. of the DHX37 gene in human genetic diseases, and its molecular mechanism is not fully understood. We searched literature databases and summarized and analyzed all the literature related to DHX37 to date, including case reports, cohort studies, and molecular mechanism studies, to comprehensively demonstrate the role of DHX37 in human genetic diseases. Sixty patients were reported to have DHX37-related 46,XY DSD, with p.R308Q, p.R674W variants being the two most common mutation hotspots, accounting for 36.67% and 11.67% of cases respectively. In DSD cohorts, DHX37 gene mutations have different detection frequencies (0.77%–45.45%), whereas in testicular regression syndrome and 46,XY gonadal dysgenesis cohorts, they have a high detection rate. The gonadal development and fertility of female (46,XX) carriers with DHX37 gene mutations are not affected; however, incomplete penetrance may be observed in males (46,XY). The treatments are primarily surgical intervention and hormone replacement therapy administered at appropriate times; however, the long-term prognosis remains unknown. Although the molecular mechanism of DHX37 mutation related 46,XY DSD is unclear, ribosome synthesis, cell cycle regulation, and the NF-κB and Wnt pathways may be affected. This review summarizes the profile of DHX37 defects in human genetic diseases.

[5] Genetic/epigenetic effects in NF1 microdeletion syndrome: beyond the haploinsufficiency, looking at the contribution of not deleted genes

  • Authors: V. Tritto, P. Bettinaglio, E. Mangano, C. Cesaretti, Federica Marasca et al.
  • Year: 2024
  • Venue: Human Genetics
  • URL: https://www.semanticscholar.org/paper/bd7d04a66e132d76fee09c3a0fa1d90e535fba9c
  • DOI: 10.1007/s00439-024-02683-0
  • PMID: 38874808
  • PMCID: 11186880
  • Citations: 3
  • Summary: This study investigates an altered expression of deletion flanking genes by qPCR in patients with type-1 NF1 deletion, and suggests a novel pathomechanism that contributes to the expression phenotype in addition to haploinsufficiency of genes located within the deletion.
  • Evidence snippets:
  • Snippet 1 (score: 0.423) > This mechanism is underestimated at constitutional level, because the presence of microdeletion mainly addresses the identification of somatic mutations of onco-suppressor genes.Moreover, NF1 is a dominant RAS pathway disorder and a variant in a second gene, encoding an interacting partner or an effector of the same pathway, can worsen the clinical phenotype, contributing to interintra-familial variable expressivity (Ferrari et al. 2020;Tritto et al. 2023a).Variants with modifier significance and subclinical effect are generally classified as polymorphisms for their presence in the normal population because they are not subjected to genetic constraint.They can be detected by NGS, even if they are generally not selected by the pipelines commonly applied for identification of pathogenic variants (Deltas 2018).Some glomerulopathies, cystic fibrosis and thalassemias are well studied examples of diseases in which the contribution of secondary functional DNA variants leads to a configuration of the final phenotype (Gallati 2014;Deltas 2018;Mettananda and Higgs 2018). > Given the highest prevalence of type-I NF1 microdeletion, among the NF1 microdeletion patients, we enrolled 22 patients, studied their clinical phenotype, and evaluated the effect of their microdeletion dissecting the role of position effect, pseudo-dominance and modifier gene variants to provide new insights into identifying the pathogenesis of NF1 microdeletion syndrome.This is a paradigmatic study aimed at increasing knowledge on the etiology of microdeletions syndromes.These results provide new insights to address genotype-phenotype correlation with a positive impact on patient's management and future development of druggable targets and the effective pharmacological therapies.

[6] Epigenetic Insights into Tuberous Sclerosis Complex, Von Hippel–Lindau Syndrome, and Ataxia–Telangiectasia

  • Authors: Gavriel Hadjigavriel, Christina Stylianides, Evangelos Axarloglou, M. Manthou, E. Vakirlis et al.
  • Year: 2025
  • Venue: Epigenomes
  • URL: https://www.semanticscholar.org/paper/5643fde916e6d150423d2be7a32508e11fb6b6f8
  • DOI: 10.3390/epigenomes9020020
  • PMID: 40558831
  • PMCID: 12191455
  • Citations: 1
  • Summary: Current evidence on the epigenetic landscape of these syndromes is consolidated, elucidating how modifications may influence disease behavior and contribute to incomplete genotype–phenotype correlations by integrating epigenetic insights with known molecular pathways.
  • Evidence snippets:
  • Snippet 1 (score: 0.421) > Neurocutaneous syndromes represent a clinically and genetically heterogeneous group of disorders, with tuberous sclerosis complex (TSC), von Hippel–Lindau syndrome (VHL), and ataxia–telangiectasia (A-T) exemplifying some of the most complex entities within this category. These syndromes have traditionally been considered monogenic disorders, caused by germline mutations in tumor suppressor or regulatory genes. However, they exhibit a striking degree of phenotypic variability and divergent clinical trajectories that cannot be fully explained by their underlying genetic alterations alone. Increasingly, epigenetic regulatory mechanisms, such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA (ncRNA) activity, are recognized as key modulators of gene expression, cellular differentiation, and tissue-specific function. Disruption of these mechanisms has been implicated in disease pathogenesis, tumorigenesis, and neurodegeneration associated with TSC, VHL, and A-T. Aberrant epigenetic profiles may underlie the observed variability in clinical outcomes, even among individuals with identical mutations. This review consolidates current evidence on the epigenetic landscape of these syndromes, elucidating how these modifications may influence disease behavior and contribute to incomplete genotype–phenotype correlations. By integrating epigenetic insights with known molecular pathways, a more nuanced understanding of disease biology emerges, with potential implications for diagnostic stratification, prognostic assessment, and therapeutic innovation.

[7] Disorders of the genome architecture: a review

  • Authors: Dhavendra Kumar
  • Year: 2008
  • Venue: Genomic Medicine
  • URL: https://www.semanticscholar.org/paper/df00164481646356263fd7a235e072cde2e723e1
  • DOI: 10.1007/s11568-009-9028-2
  • PMID: 19277903
  • Citations: 35
  • Influential citations: 3
  • Summary: Widespread application of high-resolution genome analyses may offer to detect more sporadic phenotypes resulting from genomic rearrangements involving de novo copy number variation.
  • Evidence snippets:
  • Snippet 1 (score: 0.419) > Genetic diseases are recognized to be one of the major categories of human disease. Traditionally genetic diseases are subdivided into chromosomal (numerical or structural aberrations), monogenic or Mendelian diseases, multifactorial/polygenic complex diseases and mitochondrial genetic disorders. A large proportion of these conditions occur sporadically. With the advent of newer molecular techniques, a number of new disorders and dysmorphic syndromes are delineated in detail. Some of these conditions do not conform to the conventional inheritance patterns and mechanisms are often complex and unique. Examples include submicroscopic microdeletions or microduplications, trinucleotide repeat disorders, epigenetic disorders due to genomic imprinting, defective transcription or translation due to abnormal RNA patterning and pathogenic association with single nucleotide polymorphisms and copy number variations. Among these several apparently monogenic disorders result from non-allelic homologous recombination associated with the presence of low copy number repeats on either side of the critical locus or gene cluster. The term ‘disorders of genome architecture’ is alternatively used to highlight these disorders, for example Charcot-Marie-Tooth type IA, Smith-Magenis syndrome, Neurofibromatosis type 1 and many more with an assigned OMIM number. Many of these so called genomic disorders occur sporadically resulting from largely non-recurrent de novo genomic rearrangements. Locus-specific mutation rates for genomic rearrangements appear to be two to four times greater than nucleotide-specific rates for base substitutions. Recent studies on several disease-associated recombination hotspots in male-germ cells indicate an excess of genomic rearrangements resulting in microduplications that are clinically underdiagnosed compared to microdeletion syndromes. Widespread application of high-resolution genome analyses may offer to detect more sporadic phenotypes resulting from genomic rearrangements involving de novo copy number variation.

[8] 2q37 Deletion syndrome confirmed by high-resolution cytogenetic analysis

  • Authors: Eun Kyung Cho, Jinsup Kim, A. Yang, S. Cho, D. Jin
  • Year: 2017
  • Venue: Annals of Pediatric Endocrinology & Metabolism
  • URL: https://www.semanticscholar.org/paper/a98b78d1ef24b4fc17db2b2be6ad4a12ac87741c
  • DOI: 10.6065/apem.2017.22.2.129
  • PMID: 28690993
  • PMCID: 5495980
  • Citations: 9
  • Summary: Chromosome 2q37 deletion syndrome should be considered in the differential diagnosis of patients presenting with AHO features, especially in the presence of facial dysmorphism, and high-resolution cytogenetic analysis is recommended.
  • Evidence snippets:
  • Snippet 1 (score: 0.410) > We report a Korean patient with deletion of 2q37. In the case of 2q subtelomeric deletions, significant variability in clinical presentation is apparent, but almost all patients have some degree of mental retardation and facial dysmorphism 6) . Our patient had the following features similar to the reported phenotype of 2q37 deletion: characteristic facial features, ear abnormalities, ptosis, brachydactyly, mild mental retardation, developmental delay, and short stature. Another congenital defect found in our patient was peripheral nerve palsy, but it is nonspecific for the 2q37 deletion phenotype. > Unusually, our patient suffered from DCMP without any congenital structural defects. Congenital heart malformations have been noted in up to 20% of patients with 2q37 deletions 3) . Septal defects are most common, and aortic coarctation has been described 3) . However, DCMP has not been reported in 2q37 deletion patients, and the relationship between DCMP and 2q37 deletion is not clear. Our patient presented with short stature and was diagnosed as having partial GH deficiency. To date, there have been only 3 reports of GH deficiency in patients with 2q37 deletions 6,8,9) . Two cases were confirmed as 2q37 deletions 6,9) , and 1 case was confirmed as a distal 2p duplication and 2q deletion with severe short stature and pituitary hypoplasia 8) . All 3 reports noted a significant increase in growth rate after substitutive GH therapy, as shown in our patient. > Chromosome analysis confirms the diagnosis of 2q37 microdeletion syndrome in 80%-85% of affected individuals 10) . The largest telomeric deletion is about 10 Mb, while the smallest is around 3 to 4 Mb in the 2q37 chromosomal region. size does not appear to correlate well with phenotype 11) . The size of the 2q37 deletion was 8.3 Mb in our patient. The genes involved with 2q37.1q37.3

[9] Neurodevelopmental Disorders Associated with Abnormal Gene Dosage: Smith–Magenis and Potocki–Lupski Syndromes

  • Authors: Juanita Neira-Fresneda, L. Potocki
  • Year: 2015
  • Venue: Journal of Pediatric Genetics
  • URL: https://www.semanticscholar.org/paper/ae2f935107027507a7fda71a609b1a42c7e12981
  • DOI: 10.1055/s-0035-1564443
  • PMID: 27617127
  • PMCID: 4918721
  • Citations: 51
  • Influential citations: 1
  • Summary: The neurobehavioral phenotypes of SMS and PTLS patients during different life phases are described as well as clinical guidelines for diagnosis and a multidisciplinary approach once diagnosis is confirmed by array comparative genomic hybridization or RAI1 gene sequencing.
  • Evidence snippets:
  • Snippet 1 (score: 0.409) > The proximal short arm of chromosome 17 is a genomic region that is prone to rearrangements which have been extensively characterized elsewhere. 1,2 Several distinct genomic disorders map to this region including the autosomal dominant peripheral neuropathies such as Charcot-Marie-Tooth disease type 1A (CMT1A, MIM#118220) and hereditary neuropathy with liability to pressure palsies (HNPP, MIM#162500), the chromosomal microduplication/microdeletion syndromes, Potocki-Lupski syndrome (PTLS, MIM#610883), and Smith-Magenis syndrome (SMS, MIM#182290), as well as the newly described PMP22-RAI1 duplication syndrome (Yuan et al, unpublished data, 2015). > Although haploinsufficiency of the single retinoic acidinduced gene (RAI1) is responsible for much of the phenotype in SMS, 3,4 both SMS and PTLS are examples of contiguous gene syndromes (CGS), as the clinical features of each are due to abnormal dosage and variation of physically contiguous yet functionally unrelated genes in the 17p11.2 genomic region. 5 The mechanism leading to genomic rearrangements in common microdeletion syndromes was first elucidated in SMS. 6 Interestingly, the clinical syndrome associated with duplication 17p11.2 (now known as PTLS) was initially defined based on the shared molecular structure among patients, the duplication representing the mechanistically predicted homologous recombination reciprocal of the SMS microdeletion. 7 Keywords ► congenital heart disease ► autism ► intellectual disability ► mirror traits ► gene dosage Abstract Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) are reciprocal contiguous gene syndromes within the well-characterized 17p11.2 region. Approximately 3.6 Mb microduplication of 17p11.2, known as PTLS, represents the mechanistically predicted homologous recombination reciprocal of the SMS microdeletion, both resulting in multiple congenital anomalies. Mouse model studies have revealed that the retinoic acid-inducible

[10] Spatiotemporal 7q11.23 Protein Network Implicates the GTF2I-PRKDC-DDR Pathway During Early-Fetal Brain Development in Psychiatric Diseases

  • Authors: G. Lin, Liang Chen, Weidi Wang, Wenxiang Cai, Weichen Song et al.
  • Year: 2020
  • Venue: Unknown venue
  • URL: https://www.semanticscholar.org/paper/6a2df6310ac4d8f7f3f76da6f21f8a221ebf1cce
  • DOI: 10.21203/rs.3.rs-93461/v1
  • Summary: Striatum, hippocampus, and amygdala are crucial regions for establishing connectivity between 7q11.23 proteins and their partners in early and late fetal periods, and the results suggested that GTF2I-PRKDC-DDR and GTF 2I-BRCA1-dDR pathway is crucial for the 7q 11.23 CNV genes to contribute to the pathogenesis of psychiatric diseases.
  • Evidence snippets:
  • Snippet 1 (score: 0.409) > A different approach of addressing this issue is based on creating animal or cell models to help identify the related molecular and cellular mechanisms. For instance, mice with a heterozygous deletion of GTF2I or GTF2IRD1 show defects in skeletal and craniofacial. [14]. In addition, the embryos of these mice present with a small head; this is consistent with the clinical phenotype of patients carrying a 7q11. 23 deletion. Nevertheless, the signaling pathways affected by this CNV remain unknown. > Replication factor C subunit 2 (RFC2), another 7q11.23 gene, encodes a subunit of the replication factor C (RFC) complex [15] and is known to play a role in ATR signaling [16,17]. Haploinsufficiency for RFC2 leaded to G2/M checkpoint arrest after DNA damage [18]. However, little is known about how genes with the 7q11.23 deletion/duplication may affect the occurrence of neurodevelopmental disorders because these genes are involved not only in multiple developmental stages but also within different tissues. Hence, genes exhibiting 7q11.23 deletion/duplication play different roles in different developmental stages and different anatomic structures. > CNVs have been reported to modulate gene expression, which, ultimately, might affect disease predisposition or clinical phenotypes [19,20]. Several researches have investigated CNV pathogenesis in psychiatric disorders by constructing a static topological network based on a single developmental stage [21]. Within different developmental periods, protein expression can change, as can protein-protein interactions (PPIs) [22]. Nevertheless, protein expression is a dynamic process that can occur in a different manner across different anatomical areas [23,24]. Analyses of molecular networks can reveal biological modularity and complex signaling pathways [25,26]. Previous studies discovered the pathogenesis of CNVs by constructing dynamic protein-protein interaction (PPI) networks according to alterations of protein expression in different anatomical areas and during different developmental periods [27,28]. > In addition, multiple studies mentioned above focused only on one or two genes and were unable to demonstrate how the 7q11.23 CNV is involved in brain development.

[11] Exploring pathway interactions to detect molecular mechanisms of disease: 22q11.2 deletion syndrome

  • Authors: Woosub Shin, M. Kutmon, Eleni Mina, Therese van Amelsvoort, C. Evelo et al.
  • Year: 2023
  • Venue: Orphanet Journal of Rare Diseases
  • URL: https://www.semanticscholar.org/paper/e7f38266ecbaf1d1da3e525e1969a29f36c1cddc
  • DOI: 10.1186/s13023-023-02953-6
  • PMID: 37872602
  • PMCID: 10594698
  • Citations: 3
  • Summary: The pathway interaction method was able to detect a molecular network that could possibly explain the development of neuropsychiatric diseases among the 22q11DS patients, and could be used for similar contexts, where complex genetic mechanisms need to be identified to explain the resulting phenotypic plasticity.
  • Evidence snippets:
  • Snippet 1 (score: 0.407) > Background 22q11.2 Deletion Syndrome (22q11DS) is a genetic disorder characterized by the deletion of adjacent genes at a location specified as q11.2 of chromosome 22, resulting in an array of clinical phenotypes including autistic spectrum disorder, schizophrenia, congenital heart defects, and immune deficiency. Many characteristics of the disorder are known, such as the phenotypic variability of the disease and the biological processes associated with it; however, the exact and systemic molecular mechanisms between the deleted area and its resulting clinical phenotypic expression, for example that of neuropsychiatric diseases, are not yet fully understood. Results Using previously published transcriptomics data (GEO:GSE59216), we constructed two datasets: one set compares 22q11DS patients experiencing neuropsychiatric diseases versus healthy controls, and the other set 22q11DS patients without neuropsychiatric diseases versus healthy controls. We modified and applied the pathway interaction method, originally proposed by Kelder et al. (2011), on a network created using the WikiPathways pathway repository and the STRING protein-protein interaction database. We identified genes and biological processes that were exclusively associated with the development of neuropsychiatric diseases among the 22q11DS patients. Compared with the 22q11DS patients without neuropsychiatric diseases, patients experiencing neuropsychiatric diseases showed significant overrepresentation of regulated genes involving the natural killer cell function and the PI3K/Akt signalling pathway, with affected genes being closely associated with downregulation of CRK like proto-oncogene adaptor protein. Both the pathway interaction and the pathway overrepresentation analysis observed the disruption of the same biological processes, even though the exact lists of genes collected by the two methods were different. Conclusions Using the pathway interaction method, we were able to detect a molecular network that could possibly explain the development of neuropsychiatric diseases among the 22q11DS patients. This way, our method was able to complement the pathway overrepresentation analysis, by filling the knowledge gaps on how the affected pathways are linked to the original deletion on chromosome 22. We expect our pathway interaction method could be used for problems with similar contexts, where complex genetic mechanisms need to be identified to explain the

[12] Bifocal germinoma in a patient with 16p11.2 microdeletion syndrome

  • Authors: Mara Ventura, L. Gomes, J. Rosmaninho‐Salgado, L. Barros, I. Paiva et al.
  • Year: 2019
  • Venue: Endocrinology, Diabetes & Metabolism Case Reports
  • URL: https://www.semanticscholar.org/paper/bb345cd394bfd3134b3e99373b4cbda425b4392c
  • DOI: 10.1530/EDM-18-0149
  • PMID: 30738016
  • PMCID: 6373620
  • Citations: 10
  • Summary: The first germinoma is described in a patient with a 16p11.2 deletion syndrome, raising the question about the impact of this genetic alteration on tumorigenesis and highlighting the need of molecular analysis of germ cell tumors as only little is known about their genetic background.
  • Evidence snippets:
  • Snippet 1 (score: 0.406) > microdeletion has a population prevalence of approximately 1/2000 (7) and is associated with variable clinical features that include learning difficulties/intellectual disability, social impairment, autism, delayed language, obesity/overweight and minor dysmorphic facial features (8). A variety of rare clinical features have been associated with this deletion and tumors as seminoma, cholesteatoma, desmoid tumor, leiomyoma and Wilms tumor have been described in a few patients, suggesting either fortuitous associations or low penetrance through unmasking of recessive mutations (7,9). The scarcity of ICGTs and the lack of an in-depth characterization of their genotype make it difficult to understand the true mechanisms beyond these associations. To the best of our knowledge, there are currently no studies reporting an association between 16p11.2 deletion and germ cell tumors. Therefore, we may hypothesize that this deletion may be involved in promoting cell proliferation, contributing to tumorigenesis. In fact, some of the genes within the deleted area (Table 2) are associated with cell cycle proliferation and cellular replication, namely mitogenactivated protein kinase 3 (MAPK3) (10). > The limited available data and the phenotypic heterogeneity of the syndrome are important pitfalls that need to be overcome to get a clear picture on this relationship. Future studies should evaluate the influence of additional genetic and environmental factors in shaping the phenotype of this syndrome. A comprehensive knowledge of the molecular mechanisms involved may have a relevant impact on patient's diagnosis, treatment and follow-up and may help in the management of endocrine insufficiencies, with the potential to reduce the undesirable effects of current therapeutic approaches.

[13] Novel variants in KAT6B spectrum of disorders expand our knowledge of clinical manifestations and molecular mechanisms

  • Authors: M. Yabumoto, Jessica Kianmahd, Meghna Singh, Maria F. Palafox, Angela Wei et al.
  • Year: 2021
  • Venue: Molecular Genetics & Genomic Medicine
  • URL: https://www.semanticscholar.org/paper/3a47a1b1208ba7420900b090d3d7d712ed391719
  • DOI: 10.1002/mgg3.1809
  • PMID: 34519438
  • PMCID: 8580094
  • Citations: 12
  • Influential citations: 2
  • Summary: A range of features previously described for KAT6B‐related syndromes are identified, including concern for keratoconus, sensitivity to light or noise, recurring infections, and fractures in greater numbers than previously reported.
  • Evidence snippets:
  • Snippet 1 (score: 0.403) > Finally, as gene-centric models of disease have started to take hold, understanding the underlying functional mechanisms that are affected can help us elucidate the effect on molecular and cellular phenotypes that are regulated by KAT6B (Klein et al., 2019;Sheikh et al., 2012). We developed a model of KAT6B truncating variants in a human cell line to explore how these variants result in differential regulation of key transcripts. These types of approaches have been performed in a high throughput manner for tumor suppressor genes like BRCA1 (Findlay et al., 2018) and TP53 (Kotler et al., 2018) and can help identify key pathways that are dysregulated by KAT6B-related disorders and could be future targets for translational research. > Here, we analyze 20 clinical cases representing a KAT6B-related clinical spectrum across three domains: their genotype, phenotype, and experience with genetic counseling resources. Furthermore, we developed an in vitro model of KAT6B mutations using CRISPR technology to explore the effect of protein truncation on global transcriptional regulation. Here we demonstrate that the genes that drive core clinical phenotypes are enriched in our in vitro model system. Together, we show that our clinical observations parallel the transcriptional processes in our cell model systems which allow for a further understanding of the mechanisms underlying the KAT6Brelated clinical spectrum.

[14] Retinoic Acid Induced 1, RAI1: A Dosage Sensitive Gene Related to Neurobehavioral Alterations Including Autistic Behavior

  • Authors: P. Carmona-Mora, K. Walz
  • Year: 2010
  • Venue: Current Genomics
  • URL: https://www.semanticscholar.org/paper/fd71900e9fb4ef4a9ae5290a08e485137368bdd1
  • DOI: 10.2174/138920210793360952
  • PMID: 21629438
  • PMCID: 3078685
  • Citations: 54
  • Influential citations: 5
  • Summary: The evidence of RAI1 as a dosage sensitive gene, its relationship with different neuro behavioral traits, gene structure and mutations, and what is known about its molecular and cellular function are discussed, as a first step in the elucidation of the mechanisms that relate dosage sensitive genes with abnormal neurobehavioral outcomes.
  • Evidence snippets:
  • Snippet 1 (score: 0.403) > Genomic structural changes, such as gene Copy Number Variations (CNVs) are extremely abundant in the human genome. An enormous effort is currently ongoing to recognize and catalogue human CNVs and their associations with abnormal phenotypic outcomes. Recently, several reports related neuropsychiatric diseases (i.e. autism spectrum disorders, schizophrenia, mental retardation, behavioral problems, epilepsy) with specific CNV. Moreover, for some conditions, both the deletion and duplication of the same genomic segment are related to the phenotype. Syndromes associated with CNVs (microdeletion and microduplication) have long been known to display specific neurobehavioral traits. It is important to note that not every gene is susceptible to gene dosage changes and there are only a few dosage sensitive genes. Smith-Magenis (SMS) and Potocki-Lupski (PTLS) syndromes are associated with a reciprocal microdeletion and microduplication within chromosome 17p11.2. in humans. The dosage sensitive gene responsible for most phenotypes in SMS has been identified: the Retinoic Acid Induced 1 (RAI1). Studies on mouse models and humans suggest that RAI1 is likely the dosage sensitive gene responsible for clinical features in PTLS. In addition, the human RAI1 gene has been implicated in several neurobehavioral traits as spinocerebellar ataxia (SCA2), schizophrenia and non syndromic autism. In this review we discuss the evidence of RAI1 as a dosage sensitive gene, its relationship with different neurobehavioral traits, gene structure and mutations, and what is known about its molecular and cellular function, as a first step in the elucidation of the mechanisms that relate dosage sensitive genes with abnormal neurobehavioral outcomes.

[15] A rare case of 2q37 deletion syndrome presented with patent foramen ovale

  • Authors: Ahmed Zaki, Nour Shaheen, Mohamed Hosny, Abdelraouf Ramadan, A. Nashwan
  • Year: 2023
  • Venue: Clinical Case Reports
  • URL: https://www.semanticscholar.org/paper/b207cce700c23aed157616a1ca76cb5b79cb7b21
  • DOI: 10.1002/ccr3.6970
  • PMID: 38028106
  • PMCID: 10658514
  • Citations: 1
  • Summary: This case report presents a 3‐year‐old female child diagnosed with 2q37 deletion syndrome and patent foramen ovale, and the improvement in hypotonia and gross motor delay after 1 year of physical therapy. This case highlights the importance of thorough examination and diagnostic testing in identifying underlying causes of developmental delays.
  • Evidence snippets:
  • Snippet 1 (score: 0.402) > 2q37 deletion syndrome is a genetic disorder characterized by the loss of a small portion of genetic material located on chromosome 2. The specific deletion occurs within the 2q37 region, which is located on the long q arm of chromosome 2 and is divided into three cytogenic areas containing a total of 179 genes. However, only 11 of these genes have been identified as being related to the 2q37 deletion syndrome. The amount of genetic material lost in this disorder can vary from individual to individual, and it is missing in one of the patient's two copies of chromosome 2. 1 The majority of individuals diagnosed with 2q37 microdeletion syndrome are considered to be isolated cases, meaning that they do not have a familial history of the disorder. Additionally, patients with this disorder typically exhibit a normal parental phenotype karyotype, meaning that there are no observable chromosomal abnormalities in their parents. 2 Patients diagnosed with 2q37 microdeletion syndrome may experience a range of developmental effects, which can vary greatly from individual to individual. Common symptoms in infants may include low muscle tone and feeding difficulties. Developmental delay, learning disabilities, and physical abnormalities such as brachycephaly, obesity, and digit abnormalities are also commonly observed. Some patients may also experience respiratory issues such as asthma, ear and chest infections, seizures, and autism. Facial characteristics can also vary among patients, but may include a prominent forehead, sparse flared medial eyebrows, depressed nasal bridge, Vshaped nasal tip, high-arched palate, alopecia totalis, boxy skull with prominent forehead, and up-slanting palpebrae. 3,4 In addition to the aforementioned clinical features, the 2q37 deletion syndrome has been reported to be associated with various other anomalies. Gastrointestinal anomalies such as pyloric stenosis as reported in reference, 5 and central nervous system (CNS) anomalies such as holoprosencephaly 6 have been observed in patients with this deletion syndrome.

[16] Molecular Systems Biology of Neurodevelopmental Disorders, Rett Syndrome as an Archetype

  • Authors: V. Faundez, Meghan E. Wynne, A. Crocker, D. Tarquinio
  • Year: 2019
  • Venue: Frontiers in Integrative Neuroscience
  • URL: https://www.semanticscholar.org/paper/2360989d80e21136f1bc3eb3c5c196d5a6a5a6be
  • DOI: 10.3389/fnint.2019.00030
  • PMID: 31379529
  • PMCID: 6650571
  • Citations: 16
  • Summary: It is proposed that an approach to testing the potential of systems biology to identify mechanisms and biomarkers of disease in the example of Rett syndrome can not only aid in monitoring clinical disease severity but also provide a measure of target engagement in clinical trials.
  • Evidence snippets:
  • Snippet 1 (score: 0.400) > the role of MECP2 as a transcriptional regulator, to mesoscale processes affected by the mutation, like cell and tissue mechanisms, to macroscale phenotypes at the level of circuit or anatomical brain dysfunction. 5. Animal and cellular models of disease should genetically and phenotypically reproduce disease features (Katz et al., 2012). These animal models are essential because they offer unlimited experimental access to all tissues, developmental stages, and levels of biological complexity along a pathogenesis continuum. 6. Cell and tissue analysis should not be constrained to neurons and brain tissue, even if the most salient pathology and clinical features point to the brain. This assertion is founded on the observation that most brain genes are expressed in diverse tissues (Uhlén et al., 2015). We would like to emphasize that in addition to searching for common mechanisms of disease shared among tissues, the advantage of conceptualizing disease as a systemic/multiorgan disorder is the immediate translational implication that biomarkers of disease could be explored in accessible tissues. For example, we could sample biomarkers in patient tissues, such as muscle, or fluids more accessible than the brain. Take for example genes involved in lipid and cholesterol metabolism, whose expression is controlled by MECP2 in brain cortex and liver (Buchovecky et al., 2013a;Kyle et al., 2016). The concept that organ-specific diseases express molecular phenotypes in multiple tissues other than the affected organ has been tested comprehensively in mouse models of organ-specific pathologies (Kozawa et al., 2018). > Rett syndrome fulfills some of these criteria for the search of biomarkers. However, we still know little about mesoscale cell and tissue mechanisms disrupted by MECP2 genetic defects (Katz et al., 2012). Despite this, we have a plethora of information about the most mutation-proximal mechanisms of MECP2 loss-of-function as a transcriptional regulator and the circuit consequences of MECP2 mutations (Na et al., 2013). The most proximal mechanisms to the mutation stem from the molecular function of MECP2 as a transcriptional regulator/repressor capable of inducing up-or down-regulation of gene transcription (Lyst and Bird, 2015;Chole

[17] Genomic, Clinical, and Behavioral Characterization of 15q11.2 BP1-BP2 Deletion (Burnside-Butler) Syndrome in Five Families

  • Authors: Isaac Baldwin, Robin L. Shafer, W. Hossain, S. Gunewardena, Olivia J. Veatch et al.
  • Year: 2021
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/a1552a76ef4e9aafb4a890aa484ede27b8d0346c
  • DOI: 10.3390/ijms22041660
  • PMID: 33562221
  • PMCID: 7914695
  • Citations: 13
  • Summary: Results from this study are expected to inform future research into the genetic factors influencing diverse symptoms in patients with Burnside-Butler syndrome, an emerging disorder with a neurodevelopmental behavioral phenotype.
  • Evidence snippets:
  • Snippet 1 (score: 0.400) > For example, dysfunctional variation in the NIPA1 and NIPA2 genes could impair the function of magnesium transport as both genes encode magnesium transporters [24,25]. Their biological processes and molecular functions could regulate axonogenesis and axon extension via relationships with bone morphogenetic protein (BMP) and signaling pathways, regulations of cellular and developmental growth, and interaction with the FMR1 gene causing fragile X syndrome [13]; all pertinent and relevant to the reported variable clinical phenotypes seen in this microdeletion syndrome. We used whole-exome sequence data to identify other genes outside of the deleted region with possibly damaging variants to help detect genetic effects underlying expression of symptoms in the affected child bringing the family to medical attention. Detailed physical examinations and family pedigrees were performed, for the first time, by an experienced clinical geneticist trained as a dysmorphologist to characterize the phenotype and review of systems on each subject. In addition, cognitive and behavior testing, including motor assessments for ataxia or balance disturbances of each family member, were performed using various validated techniques and tests by experts in the field. These studies were the major outcome measures for comparison with the genomic data and analysis for similarities among our families with the 15q11.2 BP1-BP2 deletion.

[18] Cytogenomic Abnormalities and Underlying Mechanisms for Intellectual and Developmental Disabilities

  • Authors: Peining Li
  • Year: 2013
  • Venue: Journal of Molecular and Genetic Medicine
  • URL: https://www.semanticscholar.org/paper/2578c174427082f0beff180c57c6414783a4601b
  • DOI: 10.4172/1747-0862.1000073
  • Citations: 1
  • Summary: Functional analyses using in vitro cellular phenotyping and in vivo animal modeling have been developed for clinically detected pCNVs and there is urgent demand for rapid transition from diagnostic discovery to study of disease-causing mechanisms and exploration of therapeutic approaches.
  • Evidence snippets:
  • Snippet 1 (score: 0.400) > For many newly detected pCNVs, little is known about the dosagesensitive genes and their cellular and developmental functions. The limited availability and accessibility of live brain and neuron tissues is the major obstacle in the study of disease-causing mechanisms in human mental development. Recent progress in stem cell technologies has made possible the modeling of human mental diseases using patient derived stem cells. In 2010, Marchetto et al. developed a culture system using induced pluripotent stem cells (iPSCs) from Rett syndrome patients' fibroblasts [8]. These Rett syndrome iPSCs were able to undergo X-inactivation and generate functional neurons. Neurons derived from these iPSCs had fewer synapses, reduced spine density, smaller soma size, altered calcium signaling and electrophysiological defects when compared to controls. This cellular model provided critical evidence of an unexplored developmental window before disease onset and enable direct testing of drug effect in rescuing synaptic defects. > The microdeletion and microduplication at the same genomic locus offer an opportunity to study dosage-sensitive genes, especially for the opposite phenotypes of haploinsufficient and triple-sensitive genes. However, clinical evaluation could be complicated by overlapped phenotypes, variable expressivity, reduced penetrance and lack of longitudinal study of late-onset phenotypes for many genomic disorders. Recent studies observed opposite phenotypes in a few genomic disorders. For example, the microdeletion syndrome at 16p11.2 (OMIM#611913) and the reciprocal microduplication syndrome (OMIM#614671) were initially associated with ASD but a subsequent study revealed mirror body mass index phenotypes. Microdeletion at 16p11.2 is often associated with obesity, macrocephaly and ASD, while the reciprocal microduplication is associated with underweight, microcephaly and schizophrenia [9]. Mouse models of 16p11.2 microdeletion and microduplication detected in vivo brain anomalies and behavior disorders [10]. Overexpression and transcript suppression of the 29 candidate genes from this 16p11.2

[19] Role of Transcriptomics in Precision Oncology

  • Authors: Ruby Srivastava
  • Year: 2024
  • Venue: Reports of Radiotherapy and Oncology
  • URL: https://www.semanticscholar.org/paper/0bd862558bbb7286336111d9dfd232b5f905d3d9
  • DOI: 10.5812/rro-142195
  • Citations: 4
  • Summary: : Transcriptome profiling is one of the most widely used approaches in the field of multiomics research. It plays a crucial role in the prognostic, diagnostic, and predictive treatment of cancer patients. Novel next-generation sequencing (NGS) technologies permit the identification of cancer biomarkers, gene signatures, and their abnormal expression, affecting oncogenic and molecular targets and novel biomarkers for cancer therapies. Multiomics studies have changed the overall understanding o...
  • Evidence snippets:
  • Snippet 1 (score: 0.399) > : Transcriptome profiling is one of the most widely used approaches in the field of multiomics research. It plays a crucial role in the prognostic, diagnostic, and predictive treatment of cancer patients. Novel next-generation sequencing (NGS) technologies permit the identification of cancer biomarkers, gene signatures, and their abnormal expression, affecting oncogenic and molecular targets and novel biomarkers for cancer therapies. Multiomics studies have changed the overall understanding of cancer and opened a precise perspective for tumor diagnostics and therapy. The use of these approaches has strengthened our understanding of disease pathophysiology and classifications at the molecular level, including specific interference with drug mechanisms of action. Still, it has limited added value in the clinical setting. The omics data on precision medicine include the application of data from genes, transcripts, and proteins for diagnosis, monitoring of diseases, risk factor determination, counseling, and development of novel therapeutics. Bioinformatics applications have expanded statistics-based analysis toward deriving molecular pathways and process models for characterizing phenotypes and drug action mechanisms. In this review, we will discuss transcriptomics and interference analysis that allows the identification of predictive biomarkers at the molecular level to test drug response and analyze the molecular process interface of disease progression-relevant pathophysiology and mechanism of action to propose predictive biomarkers.

Notes

  • This provider combines search_papers_by_relevance with snippet_search.
  • No synthesis or second-stage model call is performed.