Home / Deep Research / Hypotrichosis with Juvenile Macular Dystrophy

Hypotrichosis with Juvenile Macular Dystrophy

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Hypotrichosis with Juvenile Macular Dystrophy. Core disease mechanisms, mo...

2026-04-24
Asta MONDO:0011107 Model: Asta Scientific Corpus Retrieval 17 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Hypotrichosis with Juvenile Macular Dystrophy. Core disease mechanisms, mo...

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

  • Papers retrieved: 17
  • Snippets retrieved: 20

Relevant Papers

[1] Do you know this syndrome?*

  • Authors: Renata Hubner Frainer, Luciana Boff de Abreu, G. Pinto, A. V. E. de Carvalho, Luana Pizarro Meneghello
  • Year: 2013
  • Venue: Anais brasileiros de dermatologia
  • URL: https://www.semanticscholar.org/paper/1e70afca5e9acff065a2b79aa6aa6d2c6bc66518
  • DOI: 10.1590/S0365-05962013000100023
  • PMID: 23539021
  • PMCID: 3699942
  • Citations: 39
  • Influential citations: 2
  • Summary: Congenital hypotrichosis and Stargardt macular dystrophy are rare autosomal recessive disorder of unknown etiology respectively characterized by hair loss, macular degeneration and severe progressive vision reduction. There are few reports in the literature with this association. Studies show that the defective gene is on the chromosome I6q22.1 and involve cadherin molecule in the pathogenesis. Early recognition of these disorders often starts with hair changes and should alert the dermatolog...
  • Evidence snippets:
  • Snippet 1 (score: 0.593) > Congenital hypotrichosis and Stargardt's macular dystrophy are rare autosomal recessive disorders of unknown etiologies, characterized respectively by hair loss, macular degeneration, and precocious and progressive severe vision reduction. 1,2,3he defective gene in hypotrichosis with juvenile macular dystrophy is located on the chromosome 16q22.1.This chromosome has CDH3 gene encoding the protein P-cadherin, expressed in the retinal pigment epithelium and hair follicles.The analysis of this mutation shows that all the families involved had homozygous deletion in the DNA region of the DNA 8 of the gene CDH3.These results established the molecular etiology of hypotrichosis associated with juvenile macular dystrophy and led for the first time to a cadherin molecule in the pathogenesis of such diseases. 1targardt's macular dystrophy affects one in 10.000 people and is usually inherited as an autosomal recessive disorder.It is characterized by progressive and severe reduction of central vision, typically in the first and second decades of life. 4,5The retinal pigment epithelium and the photoreceptor layer from the macular region are the most affected sites. 3,6The decrease in visual acuity often precedes the fundus changes and depends on the age of onset of the symptoms: the later the onset, the lower the probability of visual loss. 7,8e congenital hypotrichosis can be classified as focal or diffuse.The diffuse pattern may be associated with ichthyosis, basal cell carcinoma, epidermolysis bullosa, mental retardation, epilepsy, chromosomal abnormalities, bone abnormalities, ocular and ectodermal dysplasia, and in the latter, heredity as an important causal role. 6reire-Maia has proposed a classification of ectodermal dysplasias which divides them into two groups.One of this are associated to ectodermal structural change, such as the retina. 7

[2] Current Genetics in Hair Diseases

  • Authors: Y. Shimomura
  • Year: 2013
  • Venue: Unknown venue
  • URL: https://www.semanticscholar.org/paper/98f0f630201e132295da988b63ef8eb2a4811174
  • DOI: 10.5772/54004
  • Citations: 3
  • Summary: HF development is operated through reciprocal interactions between skin epithelial cells and underlying dermal cells, and it has been shown that many signaling molecules, such as Wnt, ectodysplasin (Eda), are involved.
  • Evidence snippets:
  • Snippet 1 (score: 0.532) > these classical cadherins in the HF has been further supported by two hereditary diseases resulting from mutations in the P-cadherin gene (CDH3). First, mutations in the CDH3 gene are known to underlie hypotrichosis with juvenile macular dystrophy (HJMD; MIM 601553), which is an autosomal recessive disease characterized by sparse hair and weak eyesight due to macular dystrophy of the retina [52]. In addition, it has been reported that another disease, ectodermal dysplasia, ectrodactyly and macular dystrophy (EEM syndrome; MIM 225280), is also caused by recessively-inherited mutations in the CDH3 gene [53]. Affected individuals with EEM syndrome show common hair and eye phenotype with HJMD. > However, EEM patients also shows split hand/foot malformation (ectrodactyly), suggesting crucial roles of P-cadherin in the development of not only hair and retina, but also the limbs in humans. There are no clear genotype-phenotype correlations in CDH3 mutations, as it has been reported that a same mutation in the CDH3 gene caused HJMD in one family [54], while EEM syndrome in another family [53]. Identification of modifier gene(s) may reveal this paradox in the future. > Gap junction (GJ) is a specialized intercellular structure that provides a pathway for both metabolic and ionic coupling between adjacent cells and maintains tissue homeostasis [55]. Connexins (Cxs) are 4-pass transmembrane proteins and the major component of the GJs. Clouston syndrome (MIM 129500), also known as hidrotic ectodermal dysplasia, is an autosomal dominant condition characterized by hypotrichosis, nail dystrophy, and palmoplantar keratoderma. The disease is caused by mutations in GJB6 gene which encodes Cx30 [56]. In addition, mutations in GJB2 gene encoding Cx26 are known to underlie keratitis-ichthyosis-

[3] 58th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV 2020)

  • Authors: R. Hamilton, L. Butler, D. McCulloch, A. Mcneil, Kaleena Michael et al.
  • Year: 2020
  • Venue: Documenta Ophthalmologica. Advances in Ophthalmology
  • URL: https://www.semanticscholar.org/paper/c85a40d6317fc5066636ef6932344976b9c2dfce
  • DOI: 10.1007/s10633-020-09789-6
  • PMID: 32915376
  • PMCID: 7484607
  • Citations: 3
  • Summary: Visual electrodiagnostic tests have an important role in clinical evaluation of children with neurofibromatosis type 1 (NF1) with or without optic pathway glioma, and normal VEP responses might imply intact visual pathway function.
  • Evidence snippets:
  • Snippet 1 (score: 0.506) > For achromatopsia, clinical phase 3 treatment trials are running. Purpose Hypotrichosis with juvenile macular dystrophy (HJMD, OMIM: 601553) has been described as a rare autosomal recessive disease associated with sparse scalp hair and progressive retinal degeneration caused by CHD3 (cadherin 3) gene mutation located on 16q22.1. We report the fullfield electroretinography findings of a child with hypotrichosis and retinal dystrophy. Methods A 9 year old boy with decreased visual acuity, nyctalopia and hypotrichosis underwent complete ophthalmological examination including fundus photography, optical coherence tomography (OCT) and flash ERG. The patient was referred for genetic evaluation. Results The best corrected visual acuity was 20/200 in both eyes. Fundus evaluation showed severe atrophy of the central macular region with pigment clumping and retinal atrophy at the posterior pole in particular. Flash ERG revealed severe reduction of light-adapted and dark-adapted amplitude, the latter more prominent, indicating that the disease affected the entire retina. OCT indicated disruption and loss of inner and outer retinal layers with atrophic changes extending along the posterior pole. A homozygous c.830del mutation was demonstrated on CDH3 gene. Conclusion HJMD should be kept in mind in children with early onset retinal dystrophy and congenital hypotrichosis. ERG is indispensable for the diagnosis and may reveal generalized retinal dysfunction despite marked macular involvement. Conflict of interest: None. Purpose Understanding normal maturation of retinal function and the acquisition of normal age-related data is fundamental to detect, monitor, and understand pathologic processes that affect the paediatric retina. In the present study, we report darkadapted (DA) and light-adapted (LA) ERGs to full-field white flash stimuli including the ISCEV Standard stimuli in children and compared these to adult ERGs. Methods Thirty-two participants of European descent with normal ocular and general health were recruited to this crosssectional study.

[4] Macular dystrophies associated with Stargardt-like phenotypes

  • Authors: R. A. S. Amaral, Olivia Araújo Zin, M. V. Salles, F. Motta, J. Sallum
  • Year: 2023
  • Venue: Arquivos Brasileiros de Oftalmologia
  • URL: https://www.semanticscholar.org/paper/87b1b56d8b2886a9853c330997c5e59ddf505221
  • DOI: 10.5935/0004-2749.2021-0415
  • PMID: 36995812
  • PMCID: 11619082
  • Citations: 1
  • Summary: Macular dystrophies may have phenotypic similarities to Stargardt-like phenotype associated with other genes besides the classic ones, and these genes may be associated with pathogenic variants related to the phenotypes.
  • Evidence snippets:
  • Snippet 1 (score: 0.500) > The pharmacological modulation of the visual cycle serves as a novel approach to the potential treatment of degenerative retinal diseases. Finding the involved genes in the phenotypes leads to new possibilities of discovering treatments by increasing or decreasing the function on the metabolic pathways of those genes. As the pathophysiology of STGD1 is complex, a multitargeted approach could help in the identification of alternative pathways or modification factors involving the disease mechanism. > In this report of four patients with macular dystrophy and history suggesting Stargardt-like disease, two patient's phenotypes were related to AD genes (RIMS1 and CRX) and those of the other two patients were related to AR genes (CRB1 and RDH12). STGD1 is the most common inherited macular dystrophy but has a wide clinical spectrum, and several inherited macular dystrophies have phenotypic similarities that can make clinical diagnosis challenging. As the disease progress, clinical appearance may change over time, and its end-stage appearance of diffuse atrophy and peripheral involvement are almost indistinguishable from each other. Functional tests are still important for the characterization of the phenotype and help in the diagnostic definition, especially in cone dystrophies, which are often the main differential diagnosis for STGD1. > Molecular genetic studies and detailed clinical descriptions have demonstrated that a central atrophic lesion with surrounding subretinal yellow flecks can arise secondary to mutations in different genes. With the improvement of potential treatments for inherited retinal dystrophies, correct molecular diagnosis is essential.

[5] Genetic Hair Disorders: A Review

  • Authors: Azhar A. Ahmed, Hind M. Almohanna, Jacob Griggs, A. Tosti
  • Year: 2019
  • Venue: Dermatology and Therapy
  • URL: https://www.semanticscholar.org/paper/ecf7b5e9e6265ba893e147b651dcfa3a9623a948
  • DOI: 10.1007/s13555-019-0313-2
  • PMID: 31332722
  • PMCID: 6704196
  • Citations: 44
  • Influential citations: 2
  • Summary: Detailed history including family history and physical examination of hair and other ectodermal structures with the use of dermoscopic devices and biopsy all provide important clues to establish the correct diagnosis.
  • Evidence snippets:
  • Snippet 1 (score: 0.489) > Congenital hypotrichosis associated with juvenile macular dystrophy (MIM 601553) is a rare autosomal recessive disorder characterized by early hair loss, heralding progressive Fig. 1 Autosomal recessive woolly hair/hypotrichosis. Note sparse blond curled hair degeneration of the retinal macula leading to early blindness during the second to third decade of life [23,24]. HJMD prevalence is unknown and has only been reported in approximately 30 patients [25][26][27][28][29][30]. Sprecher et al. [23] used mapping in four consanguineous families to localize the gene defective in HJMD to 16q22.1. This region contains CDH3, encoding P-cadherin, which is expressed in the hair follicles and retinal pigment epithelium. Mutation analysis shows in all families a common homozygous deletion in exon 8 of CDH3. These findings establish for the first time the molecular etiology of HJMD and link a cadherin molecule in the pathogenesis of this hair and retinal disorder [23]. Furthermore, Indelman et al. reported another four members of a consanguineous family with HJMD. Light and scanning electron microscopy of the hair shaft revealed pili torti. Fundus examination of the eyes showed marked degeneration of the macular pigment epithelium. DNA analysis of the entire coding sequence of CDH3 revealed, in all affected individuals, a homozygous missense mutation resulting in a single amino acid substitution at position 503 of P-cadherin sequence (R503H). This is considered the first missense mutation reported in CDH3 and second mutation found to underlie HJMD [31]. > Additionally, Indelman and his colleagues assessed nine patients belonging to five families to further characterize the CDH3 mutation spectrum and delineate possible phenotype-genotype correlations. Significant inter-and intrafamilial differences in hair morphology were found, as well as differences in associated skin findings, severity, and age of onset of visual disability [32].

[6] Hypotrichosis and juvenile macular dystrophy caused by CDH3 mutation: A candidate disease for retinal gene therapy

  • Authors: Mandeep S. Singh, S. Broadgate, R. Mathur, R. Holt, S. Halford et al.
  • Year: 2016
  • Venue: Scientific Reports
  • URL: https://www.semanticscholar.org/paper/2f577720d956ea379369d53412be89b2c6c9ce40
  • DOI: 10.1038/srep23674
  • PMID: 27157923
  • PMCID: 4860587
  • Citations: 16
  • Influential citations: 1
  • Summary: The number of reported cases of HJMD is expanded and the phenotypic characteristics to consider when selecting candidates for retinal gene therapy are highlighted, which suggests the presence of a therapeutic window for gene augmentation therapy to preserve visual acuity.
  • Evidence snippets:
  • Snippet 1 (score: 0.468) > Hypotrichosis with juvenile macular dystrophy (HJMD) is an autosomal recessive disorder that causes childhood visual impairment. HJMD is caused by mutations in CDH3 which encodes cadherin-3, a protein expressed in retinal pigment epithelium (RPE) cells that may have a key role in intercellular adhesion. We present a case of HJMD and analyse its phenotypic and molecular characteristics to assess the potential for retinal gene therapy as a means of preventing severe visual loss in this condition. Longitudinal in vivo imaging of the retina showed the relative anatomical preservation of the macula, which suggested the presence of a therapeutic window for gene augmentation therapy to preserve visual acuity. The coding sequence of CDH3 fits within the packaging limit of recombinant adeno-associated virus vectors that have been shown to be safe in clinical trials and can efficiently target RPE cells. This report expands the number of reported cases of HJMD and highlights the phenotypic characteristics to consider when selecting candidates for retinal gene therapy.

[7] Hypotrichosis with juvenile macular dystrophy: a case report with molecular study.

  • Authors: Lucas Perez Vicente, S. Finzi, R. Susanna, T. Young
  • Year: 2017
  • Venue: Arquivos brasileiros de oftalmologia
  • URL: https://www.semanticscholar.org/paper/e5dbf2554d58e8a9f2190e3da17949a1f31ede41
  • DOI: 10.5935/0004-2749.20170013
  • PMID: 28380103
  • Citations: 7
  • Summary: An 11-year-old Iranian boy born with a missing left index fingernail and sparse scalp hair who later displayed macular pigmentary changes is described, who has a novel in-frame mutation that converts a lysine to a premature stop codon, altering synthesis of P-cadherin on chromosome 16q22.
  • Evidence snippets:
  • Snippet 1 (score: 0.466) > Hypotrichosis with juvenile macular dystrophy: a case report with molecular study.

[8] Hypotrichosis with juvenile macular dystrophy: Combination of whole‐genome sequencing and genome‐wide homozygosity mapping identifies a large deletion in CDH3 initially undetected by whole‐exome sequencing—A lesson from next‐generation sequencing

  • Authors: A. Saeidian, H. Vahidnezhad, L. Youssefian, Soheila Sotudeh, M. Sargazi et al.
  • Year: 2019
  • Venue: Molecular Genetics & Genomic Medicine
  • URL: https://www.semanticscholar.org/paper/890fd0b20b1a5bb93e353dc828631628beeb42de
  • DOI: 10.1002/mgg3.975
  • PMID: 31560841
  • PMCID: 6825862
  • Citations: 8
  • Summary: The genetic basis of HJMD in a large consanguineous family with 12 affected patients, 1–76 years of age, with characteristic phenotypes is explored.
  • Evidence snippets:
  • Snippet 1 (score: 0.456) > Alu-mediated deletion mutation, hypotrichosis with juvenile macular dystrophy, next-generation sequencing | 3 of 8 SAEIDIAN Et Al. mutation(s) in this family. All 298 genes within the shared 7.2 Mb ROH were interrogated manually and CDH3 was the only relevant candidate gene. However, subsequent analysis of DNA from three affected individuals by WES failed to identify a causative mutation in CDH3. Bioinformatics analysis of the WES data revealed, however, a missense variant in a closely linked gene (1.4 Mb distance), FHOD1: c.1306A>G, p.Arg436Gly. This variant was homozygous in all affected individuals and was found to be heterozygous in 18 out of the 19 obligate carriers. Bioinformatics predictions by ANNOVAR (Wang, Li, & Hakonarson, 2010) suggested this missense mutation to be pathogenic with a CADD score (Rentzsch, Witten, Cooper, Shendure, & Kircher, 2019) of 23.7 (for details of the methods, see Youssefian et al., 2019). This variant was also predicted by MutationTaster as a disease-causing variant. In attempts to confirm the pathogenicity of this FHOD1 mutation, a knock-in mouse for this variant was made by the CRISPR/ Cas9 technique at The Jackson Laboratory (Bar Harbor, Maine). However, careful examination of the mice up to several months of age, followed by complete necropsies, including histopathologic analysis of the skin, hair, and eyes, did not reveal any evidence of a disease phenotype (J. P. Sundberg, personal communication). > In further attempts to pursue the pathogenicity of the CDH3 gene whole-genome sequencing of DNA from the proband was performed, which identified a large deletion in CDH3: c.del161-811_246 + 1,044 (Figure 2b). This mutation deletes exon 3, which consists of 86 bp, predicting out of frame deletion of amino acids in the extracellular domain of P-cadherin
  • Snippet 2 (score: 0.453) > Hypotrichosis with juvenile macular dystrophy: Combination of whole‐genome sequencing and genome‐wide homozygosity mapping identifies a large deletion in CDH3 initially undetected by whole‐exome sequencing—A lesson from next‐generation sequencing

[9] Hypotrichosis with Juvenile Macular Dystrophy

  • Authors: F. Almeida, Rui Carneiro-Freitas, R. Caldas, A. P. Vieira
  • Year: 2018
  • Venue: International Journal of Trichology
  • URL: https://www.semanticscholar.org/paper/e136c67de1daf2897a4ccb25c0e4134d2a34c933
  • DOI: 10.4103/ijt.ijt_60_18
  • PMID: 30607044
  • PMCID: 6290288
  • Citations: 6
  • Summary: A case of a 4-year-old female patient diagnosed with hypotrichosis with juvenile macular dystrophy, associated with mutations in the cadherin 3 gene, resulting in the abnormal expression of P-cadherin is reported.
  • Evidence snippets:
  • Snippet 1 (score: 0.453) > How to cite this article: Almeida FT, Carneiro-Freitas R, Caldas R, Vieira AP. Hypotrichosis with juvenile macular dystrophy. Int J Trichol 2018;10:234-6.
  • Snippet 2 (score: 0.453) > Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disease, characterized by hypotrichosis and progressive macular degeneration, leading to blindness in the first three decades of life. It is associated with mutations in the cadherin 3 gene, resulting in the abnormal expression of P-cadherin. We report a case of a 4-year-old female patient diagnosed with this genodermatosis.

[10] Hypotrichosis with Juvenile Macular Dystrophy in a Patient with Cadherin 3 (CDH3) Mutation.

  • Authors: Ekta Rishi, Sugandha Goel, S. Bassi, P. Rishi
  • Year: 2022
  • Venue: Nepalese journal of ophthalmology : a biannual peer-reviewed academic journal of the Nepal Ophthalmic Society : NEPJOPH
  • URL: https://www.semanticscholar.org/paper/f7cea56be48b4874051ef2b8c509eb37f142c46d
  • DOI: 10.3126/nepjoph.v14i1.37258
  • PMID: 35996915
  • Summary: Children with reduced vision not falling into a typical macular degeneration should be examined systemically and may just have sparse scalp hair and still have a genetic disease.
  • Evidence snippets:
  • Snippet 1 (score: 0.453) > Hypotrichosis with Juvenile Macular Dystrophy in a Patient with Cadherin 3 (CDH3) Mutation.

[11] Targeted next-generation sequencing identifies ABCA4 mutations in Chinese families with childhood-onset and adult-onset Stargardt disease

  • Authors: Ling-hui Qu, Xin Jin, Chao Zeng, N. Zhou, Yan-hong Liu et al.
  • Year: 2021
  • Venue: Bioscience Reports
  • URL: https://www.semanticscholar.org/paper/e73afe36c1c96f699f6bd94e5e7121f0291d30b8
  • DOI: 10.1042/BSR20203497
  • PMID: 33988224
  • PMCID: 8173525
  • Citations: 2
  • Summary: Childhood-onset Stargardt disease was associated with severe visual loss, generalized retinal dysfunction and was due to more severe variants in ABCA4 than those found in adult-ONSet disease, expanding the existing spectrum of STGD and revealing the genotype–phenotype relationships of theABCA4 mutations in Chinese patients.
  • Evidence snippets:
  • Snippet 1 (score: 0.450) > Stargardt disease (STGD; MIM 248200) is the most common inherited juvenile onset macular dystrophy, with a prevalence of approximately 1:8000 to 1:10000, depending on the population studied [1,2].It is characterized by a decrease in central vision and the presence of bilateral atrophic-appearing foveal lesions.These lesions may have a beaten metal appearance with or without yellowish-white fundus flecks at the posterior pole or mid-peripheral retina. > STGD is mostly inherited in autosomal recessive mode, although an autosomal dominant form has been also reported [3].Mutations in ABCA4 (MIM 601691; transcript number ENSP 00000359245.3),also known as ABCR, are responsible for most cases with autosomal recessive STGD, and are also implicated in other retinal degenerative diseases such as retinitis pigmentosa type 19, cone-rod dystrophy, and age-related macular degeneration [3,4].To date, more than 1200 disease-causing mutations have been reported in ABCA4 [5].Rare cases of STGD or 'STGD-like' disease phenotypes have been reported with mutations in PRPH2, VMD2, ELOVL4, and PROM1 genes with important roles in maintaining physiological macular function [3,[6][7][8].Moreover, it should be noted that STGD or 'STGD-like' disease presents with highly variable phenotypes and progression [3,[6][7][8].Clinical features as well as onset and progression of disease can be highly variable. > STGD is particularly devastating because affected individuals lose childhood central vision, which is necessary for common tasks including reading, schooling, driving, and recognizing faces.Ongoing stem cell-based therapy [9,10] or gene therapy [11] has paved the way to clinical trials for the treatment of STGD.Therefore, accurate and comprehensive molecular diagnosis is critical as an aid to clinical diagnosis, determining the visual prognosis, offering a basis for novel therapeutic approaches, and is also crucial for prenatal diagnosis.

[12] Leber’s Congenital Amaurosis: Current Concepts of Genotype-Phenotype Correlations

  • Authors: Chu-Hsuan Huang, Chung-May Yang, Chang-Hao Yang, Yu-Chih Hou, Ta-Ching Chen
  • Year: 2021
  • Venue: Genes
  • URL: https://www.semanticscholar.org/paper/f87a83288f48c94a76177e2a04e9c52ff5c48816
  • DOI: 10.3390/genes12081261
  • PMID: 34440435
  • PMCID: 8392113
  • Citations: 74
  • Influential citations: 4
  • Summary: By reviewing the clinical course, fundoscopic images, optical coherent tomography examination, and electroretinogram, genotype-phenotype correlations could be established for common genetic mutations in LCA which would benefit the timing of the diagnosis and thus promote early intervention.
  • Evidence snippets:
  • Snippet 1 (score: 0.444) > Leber’s congenital amaurosis (LCA), one of the most severe inherited retinal dystrophies, is typically associated with extremely early onset of visual loss, nystagmus, and amaurotic pupils, and is responsible for 20% of childhood blindness. With advances in molecular diagnostic technology, the knowledge about the genetic background of LCA has expanded widely, while disease-causing variants have been identified in 38 genes. Different pathogenetic mechanisms have been found among these varieties of genetic mutations, all of which result in the dysfunction or absence of their encoded proteins participating in the visual cycle. Hence, the clinical phenotypes also exhibit extensive heterogenicity, including the course of visual impairment, involvement of the macular area, alteration in retinal structure, and residual function of the diseased photoreceptor. By reviewing the clinical course, fundoscopic images, optical coherent tomography examination, and electroretinogram, genotype-phenotype correlations could be established for common genetic mutations in LCA, which would benefit the timing of the diagnosis and thus promote early intervention. Gene therapy is promising in the management of LCA, while several clinical trials are ongoing and preliminary success has been announced, focusing on RPE65 and other common disease-causing genes. This review provides an update on the genetics, clinical examination findings, and genotype-phenotype correlations in the most well-established causative genetic mutations of LCA.

[13] Hypotrichosis with juvenile macular dystrophy: Portuguese case

  • Authors: F. Elfatoiki, F. Cordoliani, P. Regane, A. Affortit-Demoge, M. Rybojad
  • Year: 2020
  • Venue: Our Dermatology Online
  • URL: https://www.semanticscholar.org/paper/fd7033637f715f61dc9b5042be12fd4d4c1b8a75
  • DOI: 10.7241/ourd.2020e.20
  • Citations: 7
  • Summary: This dissertation aims to provide a history of ophtalmologie in France from 1910 to 1950, a period chosen in order to explore its roots as well as specific cases up to and including the year in which Adolphe de Rothschild died.
  • Evidence snippets:
  • Snippet 1 (score: 0.435) > Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder, mainly described in Israeli families of Arab Muslim origin.We report a case of this disease in portuguese family.
  • Snippet 2 (score: 0.431) > Hypotrichosis with juvenile macular dystrophy: Portuguese case

[14] How to Set Up Genetic Counselling for Inherited Macular Dystrophies: Focus on Genetic Characterization

  • Authors: R. Raimondi, F. D’Esposito, Tania Sorrentino, Panos Tsoutsanis, Francesco Paolo De Rosa et al.
  • Year: 2023
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/03e4f156766c221f495fac2ba601f6021b1cf7e5
  • DOI: 10.3390/ijms24119722
  • PMID: 37298674
  • PMCID: 10253412
  • Citations: 5
  • Summary: This review aims to provide comprehensive guidelines to enhance the genetic characterization of patients and improve counselling efficacy by combining updated literature with the authors' own experiences to contribute to the establishment of state-of-the-art genetic counselling services for inherited macular dystrophies.
  • Evidence snippets:
  • Snippet 1 (score: 0.435) > Choroidal neovascularization is a possible compliance of this condition, resembling an early onset of age-related macular dystrophy (AMD) [20]. > Sorsby Fundus Dystrophy is an autosomal dominant retinal degeneration related to the presence of pathogenic variants in the TIMP3 gene (OMIM #188826, consisting of five exons, with 39 variants reported). Visual acuity decay and metamorphopsias usually occur around the fourth to sixth decade, and choroidal neovascularizations are not uncommon [21]. > Occult Macular Dystrophy (OMD) is characterized by normal fundus appearance and progressive loss of visual acuity. The known underlying gene is dominantly inherited RP1L1 (OMIM #608581, four exons, 545 reported variants); this is also potentially a cause of RP when recessively inherited [22,23]. > The CDH3 gene (OMIM # 114021) causes a recessive form of macular dystrophy associated with hypotrichosis [24,25]. > In the complex scenario of IRDs, some genes display a marked phenotypic heterogeneity, potentially causing either distinct macular dystrophies or diffused diseases. In particular, this is the case for genes PROM1, IMPG1, FSCN2, OTX2, CRX, RAB28, and GUCA1A [26,27]. > When encountering phenotypes of macular dystrophies, differential diagnosis must be considered. This is especially the case with infectious diseases, such as toxoplasmosis (significantly resembling North Carolina MD), CMV, or toxocariasis. In addition, some systemic drugs with retinal toxicity may mimic the phenotype of an IRD, such as hydroxychloroquine, tamoxifen, and Pentosan Polysulfate Sodium [28]. These causes of similar phenotypes could be very misleading when seeking correct diagnosis and management, hence the importance of careful interviewing of the patient with ad hoc questions.

[15] Uncovering the genetic architecture of inherited retinal disease in a consanguineous Iranian cohort

  • Authors: Lieselot Vincke, K. Van Schil, H. Ahmadieh, Afrooz Moghaddasi, Hamideh Sabbaghi et al.
  • Year: 2025
  • Venue: NPJ Genomic Medicine
  • URL: https://www.semanticscholar.org/paper/a8ba76fa031c9324db053d33cd9f3ff7008423fb
  • DOI: 10.1038/s41525-025-00473-9
  • PMID: 40055385
  • PMCID: 11889135
  • Summary: This integrated study using WES and in-depth variant assessment significantly expanded the molecular spectrum of IRD in Iran, an understudied population.
  • Evidence snippets:
  • Snippet 1 (score: 0.433) > The macular aspect of this phenotype could be in line with the DRAM2-associated AR retinal dystrophy with early macular involvement 23 . However, the phenotype of F97, end-stage RP without mention of macular problems, is atypical for DRAM2-associated IRD (see Supplementary Figs. 3 and 6 for available clinical data). > A homozygous CDH3 deletion of exons 1-2 was identified in F111, a patient with early RCD with macular dystrophy. CDH3 variants, however, are associated with congenital hypotrichosis with juvenile macular dystrophy (HJMD) (OMIM #601553) 24 . Symptoms of this disease are childhood-onset and progressive macular dystrophy combined with sparse scalp hair (hypotrichosis). Interestingly, CDH3 variants have also been shown to cause CRD, with the hypotrichosis confined to hypoplastic nails only 25 . In a family of Druze origin, three siblings with a CDH3 variant were additionally identified, their phenotype was described as RP, without skin or hair abnormalities 26 . Our findings could confirm this rare association of biallelic CDH3 variants with non-syndromic RP. Clinical reexamination to exclude extra-ocular symptoms was, however, not possible. Available clinical data is included in Supplementary Fig. 7. > Biallelic variants in CEP78 are typically associated with AR CRD and hearing loss (CRDHL) (OMIM #617236). Two causal variants (c.356 C > T, p.(Ser119Leu) and c.515 T > G, p.(Ile172Arg)) in this gene were found in homozygous state in two families in this Iranian cohort. In F141, with a clinical diagnosis of CRDHL (see Supplementary Fig. 8), c.515 T > G, p.(Ile172Arg) was identified, which has already been found in patients with CRDHL 27 .

[16] The Notch signaling pathway in skeletal muscle health and disease

  • Authors: D. Vargas-Franco, R. Kalra, Isabelle Draper, C. A. Pacak, A. Asakura et al.
  • Year: 2022
  • Venue: Muscle & Nerve
  • URL: https://www.semanticscholar.org/paper/2bc32ef6a1acc95f1c31b7e3ef5a268aadda4024
  • DOI: 10.1002/mus.27684
  • PMID: 35968817
  • PMCID: 9804383
  • Citations: 37
  • Summary: The clinical syndromes associated with pathogenic variants in each of these genes, known molecular and cellular functions of their protein products with a particular focus on the Notch signaling pathway, and potential novel therapeutic targets that may emerge from further investigations of these diseases are reviewed.
  • Evidence snippets:
  • Snippet 1 (score: 0.431) > Since the landmark discovery in 1986 of DMD (dystrophin), 1 the causative gene for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), dozens of additional genes have been associated with various phenotypic subtypes of muscular dystrophy. > Common disease mechanisms across multiple subtypes have, however, been more difficult to identify, with only a few major clusters such as the dystroglycanopathies identified to date. Given the common phenotypic features within muscular dystrophy categories, such as limb-girdle muscular dystrophy (LGMD), there is a high likelihood that convergent disease mechanisms exist across more muscular dystrophy subtypes than is currently recognized. > There are therapeutic implications of identifying deeper biological ties between muscular dystrophy subtypes. In recent years, the US Food and Drug Administration (FDA) has approved several molecular and genetic therapies for neuromuscular disorders that target specific genes and even specific mutation types within those genes. These approaches are being applied to ever rarer forms of muscular dystrophies. However, proceeding through the preclinical and clinical research studies needed to attain FDA approval for a new therapy is lengthy and costly, and on the current trajectory it will be decades before molecular and genetic therapies are available for all known subtypes of muscular dystrophy. > The identification and characterization of disease mechanisms that are shared by multiple muscular dystrophy subtypes could pave the way for new pathway-based treatments that have therapeutic effects for multiple disease subtypes. 2 This has the potential to accelerate the timeline for broader therapeutic coverage of patients with muscular dystrophy, with a greater impact on the entire muscular dystrophy population. > One disease mechanism that bears further analysis is the Notch signaling pathway, which is known to maintain muscle stem cell (MuSC, also known as satellite cell) quiescence. Recently, three different muscle disease genes that are known to interact with the Notch signaling pathway have been identified: MEGF10, POGLUT1, and most recently JAG2.

[17] CDH3 gene related hypotrichosis and juvenile macular dystrophy – A case with a novel mutation

  • Authors: O. Karti, S. Abalı, Ziya Ayhan, E. Gokmeydan, Serhad Nalçaçı et al.
  • Year: 2017
  • Venue: American Journal of Ophthalmology Case Reports
  • URL: https://www.semanticscholar.org/paper/589e811bb61e9396cccb01fd06e02a803dbb5e90
  • DOI: 10.1016/j.ajoc.2017.06.007
  • PMID: 29260097
  • PMCID: 5722150
  • Citations: 14
  • Influential citations: 2
  • Summary: A 13-year-old Turkish girl who experienced gradual bilateral visual deterioration with marked hair loss was related to a novel homozygous mutation, termed c.447_467del (p.149_156del), which has significance for the future mutational analysis and genetic counseling of families with HJMD, particularly in this region.
  • Evidence snippets:
  • Snippet 1 (score: 0.431) > CDH3 gene related hypotrichosis and juvenile macular dystrophy – A case with a novel mutation

Notes

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