Temtamy Syndrome

1. Disease Information

1.1 Concise overview

C12orf57-related Temtamy syndrome (MIM 218340) is an extremely rare autosomal recessive syndromic neurodevelopmental disorder characterized by global developmental delay / intellectual disability, epilepsy, frequent corpus callosum hypoplasia/agenesis, and variable ocular anomalies including coloboma, often with autistic features, hypotonia, and dysmorphic facial features. (wang2020temtamysyndromecaused pages 1-2, akizu2013wholeexomesequencingidentifies pages 2-4, platzer2014exomesequencingidentifies pages 3-5)

Temtamy preaxial brachydactyly syndrome (TPBS; MIM 605282) is an autosomal recessive multiple-congenital-anomaly syndrome with hallmark bilateral symmetric preaxial brachydactyly and hyperphalangism, frequently accompanied by hearing loss, dental anomalies, craniofacial dysmorphism, and growth retardation; it is caused by loss-of-function mutations in CHSY1. (li2010temtamypreaxialbrachydactyly pages 1-2, li2010temtamypreaxialbrachydactyly pages 5-7, li2010temtamypreaxialbrachydactyly pages 4-5)

1.2 Key identifiers and synonyms (from retrieved sources)

• C12orf57-related Temtamy syndrome: reported as “Temtamy syndrome (MIM 218340)” in case-series literature. (wang2020temtamysyndromecaused pages 1-2, alfiya2022c12orf57pathogenicvariants pages 1-3)
• TPBS: “Temtamy preaxial brachydactyly syndrome (MIM 605282)”. (li2010temtamypreaxialbrachydactyly pages 1-2)

Common alternative names used in retrieved sources (non-exhaustive; varies by author): - “Temtamy syndrome of corpus callosum and ocular abnormalities” (as cited in a 2024 founder-mutation perspective). (marafi2024foundermutationsand pages 6-7) - “Syndromic form of intellectual disability characterized by agenesis/hypoplasia of the corpus callosum, optic/chorioretinal coloboma, and intractable seizures” (used to describe C12orf57-related disease). (platzer2014exomesequencingidentifies pages 1-2)

1.3 Evidence types

Most available disease characterization in retrieved sources is derived from: - Aggregated case series / literature reviews (e.g., compiled cohorts of 17–56+ patients) (wang2020temtamysyndromecaused pages 2-4, platzer2014exomesequencingidentifies pages 3-5) - Individual case reports (e.g., a Chinese patient with a novel C12orf57 start-codon variant) (wang2020temtamysyndromecaused pages 1-2) - Genetic-discovery family studies (consanguineous multiplex families) including functional assays for one recurrent allele (akizu2013wholeexomesequencingidentifies pages 2-4, akizu2013wholeexomesequencingidentifies pages 5-7)

2. Etiology

2.1 Disease causal factors

A) C12orf57-related Temtamy syndrome (MIM 218340)

• Cause: biallelic pathogenic variants in C12orf57, frequently affecting the translation initiation codon (start-loss). (wang2020temtamysyndromecaused pages 1-2, akizu2013wholeexomesequencingidentifies pages 2-4)
• Inheritance: autosomal recessive with segregation consistent with full penetrance within reported pedigrees. (wang2020temtamysyndromecaused pages 2-4, akizu2013wholeexomesequencingidentifies pages 2-4)

B) TPBS (MIM 605282)

• Cause: biallelic loss-of-function variants in CHSY1, encoding chondroitin synthase 1. (li2010temtamypreaxialbrachydactyly pages 1-2, li2010temtamypreaxialbrachydactyly pages 5-7)
• Inheritance: autosomal recessive, commonly reported in consanguineous families. (li2010temtamypreaxialbrachydactyly pages 1-2, sher2014anovelchsy1 pages 2-4)

2.2 Risk factors

• Consanguinity / endogamy is repeatedly observed in reported C12orf57 cases; in a compiled review of 56 patients, 49/56 (87.7%) were from consanguineous families. (wang2020temtamysyndromecaused pages 2-4)
• Geographic clustering suggests population-specific recurrence (Middle East enrichment): in Wang’s 2020 review, 54/56 (96.4%) of reported patients were from Middle Eastern countries, consistent with founder effects and ascertainment patterns. (wang2020temtamysyndromecaused pages 1-2)

2.3 Protective factors / gene–environment interactions

No protective alleles or gene–environment interactions were identified in the retrieved sources.

3. Phenotypes

3.1 C12orf57-related Temtamy syndrome: phenotype spectrum (with frequencies)

The most quantitative phenotype synthesis in retrieved sources comes from Wang 2020 (n=56 literature review) and Platzer 2014 (n=17 aggregated from 7 families). (wang2020temtamysyndromecaused pages 2-4, platzer2014exomesequencingidentifies pages 3-5)

Table: This table summarizes the main reported phenotypes of C12orf57-related Temtamy syndrome using frequencies from Wang 2020 and Platzer 2014, with related HPO suggestions. It is useful for structured phenotype annotation and for comparing feature prevalence across published case series.

Key clinical concepts (current understanding): - Neurodevelopmental impairment is universal (developmental delay 100% in Wang review). (wang2020temtamysyndromecaused pages 2-4) - Epilepsy is common (73.7% in Wang review; 88% in Platzer summary) and may be treatment-resistant in a substantial subset. (wang2020temtamysyndromecaused pages 4-6, platzer2014exomesequencingidentifies pages 3-5) - Brain imaging abnormalities frequently involve the corpus callosum; Akizu described variable severity from hypoplasia to agenesis within and across families. (akizu2013wholeexomesequencingidentifies pages 2-4) - Ocular involvement may include coloboma (14.5% in Wang review; 29% in Platzer summary). (wang2020temtamysyndromecaused pages 4-6, platzer2014exomesequencingidentifies pages 3-5)

3.2 Age of onset, progression, severity

• C12orf57-related disease is typically early onset. In the Platzer aggregated series, where specified, seizure onset occurred by ≤3 years (9/9). (platzer2014exomesequencingidentifies pages 3-5)
• Severity is variable, including within families, which has been proposed to relate to hypomorphic effects of start-codon variants that reduce (rather than abolish) protein production. (akizu2013wholeexomesequencingidentifies pages 5-7)

3.3 TPBS: phenotype spectrum (qualitative)

TPBS has a distinct phenotype dominated by limb development anomalies: - “Typical preaxial brachydactyly of digits 1–3” with hyper- and symphalangism, duplicated phalanges/metatarsals, and additional skeletal anomalies (radio-ulnar synostosis, carpal/tarsal fusions). (li2010temtamypreaxialbrachydactyly pages 2-4, li2010temtamypreaxialbrachydactyly pages 4-5) - Syndromic features include facial dysmorphism, dental anomalies, growth retardation/short stature, and frequent sensorineural hearing loss. (li2010temtamypreaxialbrachydactyly pages 1-2, sher2014anovelchsy1 pages 2-4)

3.4 Quality-of-life impact

No standardized QoL instruments (e.g., EQ-5D, PROMIS) were identified in retrieved sources. However, the high rates of absent speech, severe ID, and refractory seizures indicate substantial functional impact in C12orf57-related disease. (wang2020temtamysyndromecaused pages 2-4, platzer2014exomesequencingidentifies pages 3-5)

4. Genetic / Molecular Information

4.1 Causal genes

• C12orf57 (Temtamy syndrome; MIM 218340). (wang2020temtamysyndromecaused pages 1-2, akizu2013wholeexomesequencingidentifies pages 2-4)
• CHSY1 (TPBS; MIM 605282). (li2010temtamypreaxialbrachydactyly pages 1-2)

4.2 Pathogenic variants (examples with evidence)

Table: This table summarizes key pathogenic variants reported for the two distinct entities often called Temtamy syndrome: C12orf57-related Temtamy syndrome and CHSY1-related Temtamy preaxial brachydactyly syndrome. It highlights variant class, segregation, founder evidence, and functional support using only the gathered evidence snippets.

Notable quantitative variant statistics (C12orf57-related): - In Wang’s 2020 review of 56 patients, c.1A>G was the most frequent reported variant (45/56; 80.3%). (wang2020temtamysyndromecaused pages 4-6)

Evidence supporting loss-of-function: - For C12orf57 start-codon variant c.1A>G, Akizu showed the mutant AUG→GUG start can still initiate translation but produces markedly reduced protein levels, consistent with a loss-of-function/hypomorphic mechanism. (akizu2013wholeexomesequencingidentifies pages 5-7)

4.3 Modifier genes / epigenetic information

No modifier genes or epigenetic mechanisms specific to Temtamy syndrome were identified in retrieved sources.

4.4 Chromosomal abnormalities (Temtamy-like)

A 2003 report described a Temtamy-like phenotype (callosal agenesis, colobomas, profound ID, hearing loss) with a de novo balanced translocation t(2;9)(p24;q32), highlighting historical locus-mapping approaches and the possibility of chromosomal disruption in Temtamy-like presentations. (talisetti2003temtamy‐likesyndromeassociated pages 1-3)

5. Environmental Information

No environmental, lifestyle, toxicant, or infectious causal factors were identified in the retrieved sources. These syndromes are primarily genetic. (wang2020temtamysyndromecaused pages 1-2, li2010temtamypreaxialbrachydactyly pages 1-2)

6. Mechanism / Pathophysiology

6.1 C12orf57-related Temtamy syndrome (proposed mechanism; limited mechanistic detail available)

Causal chain (supported components): 1. Biallelic C12orf57 variants (often start-loss) → 2. Reduced C12orf57 protein levels (experimental evidence for c.1A>G) and cytoplasmic localization of the protein → 3. Disrupted neurodevelopmental processes required for corpus callosum development and broader brain development → 4. Clinical manifestations: callosal hypoplasia/agenesis, seizures/epilepsy, developmental delay/ID, autistic features, and ocular anomalies. (akizu2013wholeexomesequencingidentifies pages 5-7, akizu2013wholeexomesequencingidentifies pages 2-4)

Functional notes: - Akizu found the major neural transcript to be highly enriched in fetal brain and concluded the gene is “required for development of the human corpus callosum,” but molecular pathways remain poorly defined. (akizu2013wholeexomesequencingidentifies pages 5-7, akizu2013wholeexomesequencingidentifies pages 1-2) - A 2024 cerebral organoid/ribosome study (preprint) described C12orf57 as “an important factor for early brain development” and noted that its mRNA contains a TOP-like element, making its translation sensitive to ribosome availability and global translation state; this is a mechanistic clue at the level of translational regulation rather than disease-specific causation. (ni2024aninappropriatedecline pages 13-17)

Suggested GO / CL terms (hypothesis-generating; not explicitly asserted in sources): - GO (process): corpus callosum development; regulation of translation; neurogenesis. - CL (cell types, based on organoid discussion): radial glia / neural progenitor cells (mentioned as impacted in organoid study). (ni2024aninappropriatedecline pages 13-17)

6.2 TPBS (CHSY1) mechanism: chondroitin sulfate biosynthesis with BMP/NOTCH crosstalk

Causal chain (supported components): 1. Biallelic CHSY1 loss-of-function → 2. Impaired chondroitin sulfate biosynthesis (CHSY1 provides enzymatic activities needed to build CS repeating disaccharides) → 3. Perturbed extracellular matrix/proteoglycan-mediated developmental signaling and morphogenesis → 4. Limb/digit, craniofacial, and inner-ear developmental anomalies consistent with TPBS. (li2010temtamypreaxialbrachydactyly pages 5-7)

Pathways and processes: - BMP signaling: CHSY1/chsy1 is described as a “potential target of BMP signaling,” with zebrafish data indicating BMP signaling negatively regulates chsy1 expression and BMP pathway perturbations phenocopy chsy1 knockdown. (li2010temtamypreaxialbrachydactyly pages 5-7, li2010temtamypreaxialbrachydactyly pages 1-2) - NOTCH signaling: A separate 2010 study proposed that CHSY1 inhibits NOTCH extracellularly via a Fringe domain and that loss leads to increased Notch signaling (e.g., jag2 upregulation; lim1 silencing) contributing to abnormal ossification/patterning. (tian2010lossofchsy1 pages 9-10, tian2010lossofchsy1 pages 8-9)

Suggested GO / CL / pathway terms (supported directionally by the above): - GO (process): glycosaminoglycan biosynthetic process; cartilage development; limb development; Notch signaling pathway; BMP signaling pathway. - CL (cell types): chondrocytes; inner-ear sensory epithelium/hair-cell–adjacent epithelium (zebrafish expression in chondrocytes and inner ear). (li2010temtamypreaxialbrachydactyly pages 5-7)

7. Anatomical Structures Affected

C12orf57-related Temtamy syndrome

• CNS: corpus callosum (hypoplasia/agenesis), thalamic/ventricular abnormalities described in family studies. (akizu2013wholeexomesequencingidentifies pages 2-4)
• Suggested UBERON: corpus callosum; thalamus; lateral ventricle; third ventricle.
• Eye: optic/chorioretinal coloboma and other ocular anomalies. (platzer2014exomesequencingidentifies pages 3-5, wang2020temtamysyndromecaused pages 4-6)
• Suggested UBERON: retina; choroid; optic nerve.
• Heart: atrial septal defects reported in an aggregated case review. (wang2020temtamysyndromecaused pages 4-6)

TPBS (CHSY1)

• Limbs/digits: preaxial digits 1–3 (hands/feet), metacarpals/metatarsals, carpal/tarsal bones. (li2010temtamypreaxialbrachydactyly pages 4-5)
• Auditory system: sensorineural hearing impairment is frequent. (li2010temtamypreaxialbrachydactyly pages 4-5)

8. Temporal Development

C12orf57-related Temtamy syndrome

• Onset: congenital/infancy presentation with developmental delay; seizures typically begin in early childhood and may start in infancy. (wang2020temtamysyndromecaused pages 1-2, platzer2014exomesequencingidentifies pages 3-5)
• Course: chronic lifelong neurodevelopmental disability; seizure control is variable, with a substantial refractory subset. (wang2020temtamysyndromecaused pages 4-6, platzer2014exomesequencingidentifies pages 3-5)

TPBS

• Onset: congenital limb malformations are present at birth (by definition of brachydactyly/hyperphalangism syndrome). (li2010temtamypreaxialbrachydactyly pages 1-2)

9. Inheritance and Population

C12orf57-related Temtamy syndrome

• Inheritance: autosomal recessive with frequent consanguinity. (akizu2013wholeexomesequencingidentifies pages 2-4, wang2020temtamysyndromecaused pages 2-4)
• Founder effect: Platzer explicitly states that the recurrent c.1A>G (p.Met1?) observed in Arab-descent patients “strongly suggests a founder effect within the Arab population.” (platzer2014exomesequencingidentifies pages 3-5)
• Epidemiology: prevalence/incidence not available in retrieved sources. However, case aggregation provides a minimal evidence base:
• Wang 2020 summarized 56 reported patients with C12orf57 pathogenic variants at that time. (wang2020temtamysyndromecaused pages 2-4)
• Platzer 2014 summarized 17 patients from 7 families (as-of their publication). (platzer2014exomesequencingidentifies pages 3-5)

TPBS

• Inheritance: autosomal recessive. (li2010temtamypreaxialbrachydactyly pages 1-2)
• Epidemiology: not available in retrieved sources.

10. Diagnostics

10.1 Clinical evaluation (C12orf57-related)

Common diagnostic components described across reports include: - Neurologic assessment and EEG for seizures. (wang2020temtamysyndromecaused pages 1-2, talisetti2003temtamy‐likesyndromeassociated pages 1-3) - Brain MRI to assess corpus callosum and ventricles. (wang2020temtamysyndromecaused pages 1-2, akizu2013wholeexomesequencingidentifies pages 2-4) - Ophthalmologic evaluation for coloboma/microphthalmia. (wang2020temtamysyndromecaused pages 4-6, talisetti2003temtamy‐likesyndromeassociated pages 1-3) - Cardiac evaluation (e.g., ASD/VSD) when indicated. (wang2020temtamysyndromecaused pages 4-6)

10.2 Genetic testing

• Whole-exome sequencing (WES) is repeatedly used to identify causal C12orf57 variants in affected children and families, with segregation analysis by Sanger sequencing. (wang2020temtamysyndromecaused pages 2-4, akizu2013wholeexomesequencingidentifies pages 2-4)
• A representative filtering/interpretation pipeline (depth thresholds, population frequency filters, in silico predictors, Sanger confirmation) is described in Wang 2020. (wang2020temtamysyndromecaused pages 2-4)

10.3 Differential diagnosis

Not comprehensively addressed in retrieved sources; however, historical “Temtamy-like” reports stress that overlapping syndromes with corpus callosum agenesis and ocular colobomas exist, and chromosomal abnormalities can produce similar phenotypes. (talisetti2003temtamy‐likesyndromeassociated pages 1-3)

11. Outcome / Prognosis

C12orf57-related Temtamy syndrome

• Quantitative outcome data are limited, but severe neurodevelopmental impairment is common: severe ID in 11/11 where specified in Platzer’s cohort summary and absent speech in a majority. (platzer2014exomesequencingidentifies pages 3-5)
• Seizure prognosis is variable: Wang 2020 cites a substantial refractory proportion and a relatively small seizure-free fraction in historical cases. (wang2020temtamysyndromecaused pages 4-6)

No survival curves or life expectancy estimates were identified in retrieved sources.

12. Treatment

12.1 Pharmacotherapy

• Antiseizure medications are the primary disease-directed therapy described. In a single C12orf57-related case report, oxcarbazepine dosing was escalated and the child was reported “seizure-free for 1 month” during follow-up; this illustrates symptomatic management rather than disease modification. (wang2020temtamysyndromecaused pages 1-2)

MAXO suggestions (general, not explicitly in sources): anticonvulsant therapy; developmental therapy; supportive care.

12.2 Supportive/rehabilitative care

• Given the high rates of developmental delay, hypotonia, and absent speech, supportive therapies (PT/OT/speech therapy) are implied but not described quantitatively in retrieved sources.

12.3 Clinical trials / advanced therapeutics

• No disease-specific interventional clinical trials were identified in this run. (clinical-trials search returned none relevant)

13. Prevention

• Primary prevention is not applicable for a monogenic disorder in the usual sense, but genetic counseling and carrier testing are directly relevant due to autosomal recessive inheritance, particularly in consanguineous families. (wang2020temtamysyndromecaused pages 2-4)
• Secondary prevention: early identification of seizures and developmental issues to initiate symptomatic therapies.
• Reproductive options: prenatal/preimplantation genetic testing is not explicitly discussed in retrieved sources, but the literature emphasizes segregation testing and recurrence risk awareness. (wang2020temtamysyndromecaused pages 2-4)

14. Other Species / Natural Disease

No naturally occurring non-human disease analogs were identified in retrieved sources.

15. Model Organisms

C12orf57-related Temtamy syndrome

• Akizu reports conservation and notes a fly RNAi screen where knockdown of the fly ortholog produced a nonspecific “malformation death” phenotype in ~50% of treated flies, but without a detailed phenotypic match to human disease. (akizu2013wholeexomesequencingidentifies pages 7-8)
• A 2024 human cerebral organoid study (preprint) provides mechanistic context regarding translation sensitivity of TOP-like transcripts including C12orf57, but is not a Temtamy syndrome disease model per se. (ni2024aninappropriatedecline pages 13-17)

TPBS (CHSY1)

• Zebrafish morphants: multiple studies show chsy1 knockdown produces developmental defects, including skeletal/jaw defects, pectoral fin defects (~65%), and ocular anomalies (>50%), partially phenocopying human TPBS and supporting conserved developmental roles. (li2010temtamypreaxialbrachydactyly pages 1-2, tian2010lossofchsy1 pages 8-9)

Recent developments (prioritized 2023–2024)

1. Founder mutation framing (2024): A Disease Models & Mechanisms Perspective highlights that some rare diseases in Arab populations may be largely driven by founder variants and lists C12ORF57 among such examples; it also cites “Temtamy syndrome of corpus callosum and ocular abnormalities” in its reference list. This is interpretive/public-health context rather than new mechanistic or variant discovery. (marafi2024foundermutationsand pages 4-5, marafi2024foundermutationsand pages 6-7)
2. Variant recurrence in modern cohorts (2024): A Frontiers in Genetics ASD cohort reports segregation of a homozygous C12orf57 start-codon variant (c.A1G/p.M1V; CADD 21.9) in affected siblings and notes prior reporting in consanguineous Saudi/Kuwaiti patients with global developmental delay, autism, and epilepsy—demonstrating continuing clinical relevance of this recurrent allele in Middle Eastern populations. (alsarraj2024thegeneticlandscape pages 10-11)
3. Systems-level translational regulation (2024 preprint): A bioRxiv study suggests C12orf57 is among transcripts with TOP-like motifs whose translation is sensitive to ribosome availability during early neurodevelopment in cerebral organoids. This provides a plausible mechanistic clue for why reduced C12orf57 dosage might be impactful in neurodevelopment, but it does not establish a Temtamy-specific pathway. (ni2024aninappropriatedecline pages 13-17)
4. High-throughput 5′UTR functional screening (2023 preprint): A medRxiv study included C12orf57 among genes screened for 5′UTR variant effects on translation, but the authors report they could not validate endogenous protein changes for C12orf57 due to antibody limitations (no correct-sized band), so it does not provide definitive new functional findings for C12orf57. (plassmeyer2023amassivelyparallel pages 21-23, plassmeyer2023amassivelyparallel pages 32-35)

Real-world applications / implementations

• Clinical genomics (WES) as standard-of-care for heterogeneous syndromic neurodevelopmental disorders: Multiple Temtamy syndrome diagnoses in the retrieved literature were enabled by WES with segregation testing, illustrating real-world deployment of genomic diagnostics in rare disease. (wang2020temtamysyndromecaused pages 2-4, akizu2013wholeexomesequencingidentifies pages 2-4)
• Population genetics / founder mutation programs: The 2024 founder-mutation perspective and the continued observation of recurrent C12orf57 start-codon variants in Middle Eastern pedigrees support the utility of region-specific carrier screening and counseling strategies (conceptual; implementation details not provided in retrieved sources). (marafi2024foundermutationsand pages 4-5, platzer2014exomesequencingidentifies pages 3-5)

Data gaps / limitations of this report

• MONDO/Orphanet/ICD/MeSH identifiers and prevalence/incidence were not available from the retrieved texts in this run.
• No disease-specific guidelines, standardized clinical criteria, or interventional trials were identified in the retrieved sources.
• Mechanistic understanding of C12orf57 remains limited; available evidence primarily supports loss-of-function via reduced protein dosage, with emerging hints about translation regulation sensitivity. (akizu2013wholeexomesequencingidentifies pages 5-7, ni2024aninappropriatedecline pages 13-17)

Appendix: Key quoted statements from abstracts / key excerpts (as requested)

• C12orf57 start-codon functional effect: the mutant allele “was able to produce some protein, although less efficiently than the wild-type” and “Cells transduced with the mutant construct show notably reduced protein levels.” (akizu2013wholeexomesequencingidentifies pages 5-7)
• Founder effect statement (C12orf57 c.1A>G): recurrent observation “strongly suggests a founder effect within the Arab population.” (platzer2014exomesequencingidentifies pages 3-5)
• Diagnostic yield and phenotype frequencies (Wang 2020 review): developmental delay 56/56 (100%), seizures 41/56 (73.7%), hypotonia 40/56 (71.9%), autistic behavior 40/55 (72.7%). (wang2020temtamysyndromecaused pages 2-4)

Retrieved figure/table evidence

• Wang 2020 includes a table summarizing clinical-feature frequencies and variants across 56 reported cases, and a pedigree/variant figure; these were retrieved as images in this run. (wang2020temtamysyndromecaused media b3d8bfd5, wang2020temtamysyndromecaused media 805b1c71, wang2020temtamysyndromecaused media 21e24220)

References

1. (wang2020temtamysyndromecaused pages 1-2): Yanqin Wang, Ming Li, Yuanyuan Luo, Xin Zhao, Shuang Liao, Li Jiang, Xiujuan Li, and Min Zhong. Temtamy syndrome caused by a new c12orf57 variant in a chinese boy, including pedigree analysis and literature review. Experimental and therapeutic medicine, 19 1:327-332, Nov 2020. URL: https://doi.org/10.3892/etm.2019.8183, doi:10.3892/etm.2019.8183. This article has 8 citations and is from a peer-reviewed journal.

2. (li2010temtamypreaxialbrachydactyly pages 1-2): Yun Li, Kathrin Laue, Samia Temtamy, Mona Aglan, L. Damla Kotan, Gökhan Yigit, Husniye Canan, Barbara Pawlik, Gudrun Nürnberg, Emma L. Wakeling, Oliver W. Quarrell, Ingelore Baessmann, Matthew B. Lanktree, Mustafa Yilmaz, Robert A. Hegele, Khalda Amr, Klaus W. May, Peter Nürnberg, A. Kemal Topaloglu, Matthias Hammerschmidt, and Bernd Wollnik. Temtamy preaxial brachydactyly syndrome is caused by loss-of-function mutations in chondroitin synthase 1, a potential target of bmp signaling. The American Journal of Human Genetics, 87:757-767, Dec 2010. URL: https://doi.org/10.1016/j.ajhg.2010.10.003, doi:10.1016/j.ajhg.2010.10.003. This article has 89 citations.

3. (akizu2013wholeexomesequencingidentifies pages 2-4): Naiara Akizu, Nuri M. Shembesh, Tawfeg Ben-Omran, Laila Bastaki, Asma Al-Tawari, Maha S. Zaki, Roshan Koul, Emily Spencer, Rasim Ozgur Rosti, Eric Scott, Elizabeth Nickerson, Stacey Gabriel, Gilberto da Gente, Jiang Li, Matthew A. Deardorff, Laura K. Conlin, Margaret A. Horton, Elaine H. Zackai, Elliott H. Sherr, and Joseph G. Gleeson. Whole-exome sequencing identifies mutated c12orf57 in recessive corpus callosum hypoplasia. American journal of human genetics, 92 3:392-400, Mar 2013. URL: https://doi.org/10.1016/j.ajhg.2013.02.004, doi:10.1016/j.ajhg.2013.02.004. This article has 43 citations and is from a highest quality peer-reviewed journal.

4. (platzer2014exomesequencingidentifies pages 3-5): Konrad Platzer, Irina Hüning, Carolin Obieglo, Thomas Schwarzmayr, Rainer Gabriel, Tim M. Strom, Gabriele Gillessen‐Kaesbach, and Frank J. Kaiser. Exome sequencing identifies compound heterozygous mutations in c12orf57 in two siblings with severe intellectual disability, hypoplasia of the corpus callosum, chorioretinal coloboma, and intractable seizures. American Journal of Medical Genetics Part A, 164:1976-1980, Aug 2014. URL: https://doi.org/10.1002/ajmg.a.36592, doi:10.1002/ajmg.a.36592. This article has 14 citations.

5. (akizu2013wholeexomesequencingidentifies pages 5-7): Naiara Akizu, Nuri M. Shembesh, Tawfeg Ben-Omran, Laila Bastaki, Asma Al-Tawari, Maha S. Zaki, Roshan Koul, Emily Spencer, Rasim Ozgur Rosti, Eric Scott, Elizabeth Nickerson, Stacey Gabriel, Gilberto da Gente, Jiang Li, Matthew A. Deardorff, Laura K. Conlin, Margaret A. Horton, Elaine H. Zackai, Elliott H. Sherr, and Joseph G. Gleeson. Whole-exome sequencing identifies mutated c12orf57 in recessive corpus callosum hypoplasia. American journal of human genetics, 92 3:392-400, Mar 2013. URL: https://doi.org/10.1016/j.ajhg.2013.02.004, doi:10.1016/j.ajhg.2013.02.004. This article has 43 citations and is from a highest quality peer-reviewed journal.

6. (wang2020temtamysyndromecaused pages 4-6): Yanqin Wang, Ming Li, Yuanyuan Luo, Xin Zhao, Shuang Liao, Li Jiang, Xiujuan Li, and Min Zhong. Temtamy syndrome caused by a new c12orf57 variant in a chinese boy, including pedigree analysis and literature review. Experimental and therapeutic medicine, 19 1:327-332, Nov 2020. URL: https://doi.org/10.3892/etm.2019.8183, doi:10.3892/etm.2019.8183. This article has 8 citations and is from a peer-reviewed journal.

7. (platzer2014exomesequencingidentifies pages 2-3): Konrad Platzer, Irina Hüning, Carolin Obieglo, Thomas Schwarzmayr, Rainer Gabriel, Tim M. Strom, Gabriele Gillessen‐Kaesbach, and Frank J. Kaiser. Exome sequencing identifies compound heterozygous mutations in c12orf57 in two siblings with severe intellectual disability, hypoplasia of the corpus callosum, chorioretinal coloboma, and intractable seizures. American Journal of Medical Genetics Part A, 164:1976-1980, Aug 2014. URL: https://doi.org/10.1002/ajmg.a.36592, doi:10.1002/ajmg.a.36592. This article has 14 citations.

8. (wang2020temtamysyndromecaused pages 2-4): Yanqin Wang, Ming Li, Yuanyuan Luo, Xin Zhao, Shuang Liao, Li Jiang, Xiujuan Li, and Min Zhong. Temtamy syndrome caused by a new c12orf57 variant in a chinese boy, including pedigree analysis and literature review. Experimental and therapeutic medicine, 19 1:327-332, Nov 2020. URL: https://doi.org/10.3892/etm.2019.8183, doi:10.3892/etm.2019.8183. This article has 8 citations and is from a peer-reviewed journal.

9. (li2010temtamypreaxialbrachydactyly pages 2-4): Yun Li, Kathrin Laue, Samia Temtamy, Mona Aglan, L. Damla Kotan, Gökhan Yigit, Husniye Canan, Barbara Pawlik, Gudrun Nürnberg, Emma L. Wakeling, Oliver W. Quarrell, Ingelore Baessmann, Matthew B. Lanktree, Mustafa Yilmaz, Robert A. Hegele, Khalda Amr, Klaus W. May, Peter Nürnberg, A. Kemal Topaloglu, Matthias Hammerschmidt, and Bernd Wollnik. Temtamy preaxial brachydactyly syndrome is caused by loss-of-function mutations in chondroitin synthase 1, a potential target of bmp signaling. The American Journal of Human Genetics, 87:757-767, Dec 2010. URL: https://doi.org/10.1016/j.ajhg.2010.10.003, doi:10.1016/j.ajhg.2010.10.003. This article has 89 citations.

10. (li2010temtamypreaxialbrachydactyly pages 4-5): Yun Li, Kathrin Laue, Samia Temtamy, Mona Aglan, L. Damla Kotan, Gökhan Yigit, Husniye Canan, Barbara Pawlik, Gudrun Nürnberg, Emma L. Wakeling, Oliver W. Quarrell, Ingelore Baessmann, Matthew B. Lanktree, Mustafa Yilmaz, Robert A. Hegele, Khalda Amr, Klaus W. May, Peter Nürnberg, A. Kemal Topaloglu, Matthias Hammerschmidt, and Bernd Wollnik. Temtamy preaxial brachydactyly syndrome is caused by loss-of-function mutations in chondroitin synthase 1, a potential target of bmp signaling. The American Journal of Human Genetics, 87:757-767, Dec 2010. URL: https://doi.org/10.1016/j.ajhg.2010.10.003, doi:10.1016/j.ajhg.2010.10.003. This article has 89 citations.

11. (li2010temtamypreaxialbrachydactyly pages 5-7): Yun Li, Kathrin Laue, Samia Temtamy, Mona Aglan, L. Damla Kotan, Gökhan Yigit, Husniye Canan, Barbara Pawlik, Gudrun Nürnberg, Emma L. Wakeling, Oliver W. Quarrell, Ingelore Baessmann, Matthew B. Lanktree, Mustafa Yilmaz, Robert A. Hegele, Khalda Amr, Klaus W. May, Peter Nürnberg, A. Kemal Topaloglu, Matthias Hammerschmidt, and Bernd Wollnik. Temtamy preaxial brachydactyly syndrome is caused by loss-of-function mutations in chondroitin synthase 1, a potential target of bmp signaling. The American Journal of Human Genetics, 87:757-767, Dec 2010. URL: https://doi.org/10.1016/j.ajhg.2010.10.003, doi:10.1016/j.ajhg.2010.10.003. This article has 89 citations.

12. (sher2014anovelchsy1 pages 2-4): Gulab Sher and Muhammad Naeem. A novel chsy1 gene mutation underlies temtamy preaxial brachydactyly syndrome in a pakistani family. European journal of medical genetics, 57 1:21-4, Jan 2014. URL: https://doi.org/10.1016/j.ejmg.2013.11.001, doi:10.1016/j.ejmg.2013.11.001. This article has 28 citations and is from a peer-reviewed journal.

13. (tian2010lossofchsy1 pages 9-10): Jing Tian, Ling Ling, Mohammad Shboul, Hane Lee, Brian O'Connor, Barry Merriman, Stanley F. Nelson, Simon Cool, Osama H. Ababneh, Azmy Al-Hadidy, Amira Masri, Hanan Hamamy, and Bruno Reversade. Loss of chsy1, a secreted fringe enzyme, causes syndromic brachydactyly in humans via increased notch signaling. American journal of human genetics, 87 6:768-78, Dec 2010. URL: https://doi.org/10.1016/j.ajhg.2010.11.005, doi:10.1016/j.ajhg.2010.11.005. This article has 121 citations and is from a highest quality peer-reviewed journal.

14. (sher2014anovelchsy1 pages 4-4): Gulab Sher and Muhammad Naeem. A novel chsy1 gene mutation underlies temtamy preaxial brachydactyly syndrome in a pakistani family. European journal of medical genetics, 57 1:21-4, Jan 2014. URL: https://doi.org/10.1016/j.ejmg.2013.11.001, doi:10.1016/j.ejmg.2013.11.001. This article has 28 citations and is from a peer-reviewed journal.

15. (alfiya2022c12orf57pathogenicvariants pages 1-3): F. Alfiya, Manna Jose, Soumya V. Chandrasekharan, Soumya Sundaram, Madhusoodanan Urulangodi, Bejoy Thomas, Ashalatha Radhakrishnan, Moinak Banerjee, and Ramshekhar N. Menon. C12orf57 pathogenic variants: a unique cause of developmental encephalopathy in a south indian child. Journal of Genetics, Jun 2022. URL: https://doi.org/10.1007/s12041-022-01371-0, doi:10.1007/s12041-022-01371-0. This article has 5 citations and is from a peer-reviewed journal.

16. (marafi2024foundermutationsand pages 6-7): Dana Marafi. Founder mutations and rare disease in the arab world. Disease Models & Mechanisms, Jun 2024. URL: https://doi.org/10.1242/dmm.050715, doi:10.1242/dmm.050715. This article has 18 citations and is from a domain leading peer-reviewed journal.

17. (platzer2014exomesequencingidentifies pages 1-2): Konrad Platzer, Irina Hüning, Carolin Obieglo, Thomas Schwarzmayr, Rainer Gabriel, Tim M. Strom, Gabriele Gillessen‐Kaesbach, and Frank J. Kaiser. Exome sequencing identifies compound heterozygous mutations in c12orf57 in two siblings with severe intellectual disability, hypoplasia of the corpus callosum, chorioretinal coloboma, and intractable seizures. American Journal of Medical Genetics Part A, 164:1976-1980, Aug 2014. URL: https://doi.org/10.1002/ajmg.a.36592, doi:10.1002/ajmg.a.36592. This article has 14 citations.

18. (alsarraj2024thegeneticlandscape pages 10-11): Yasser Al-Sarraj, Rowaida Z. Taha, Eman Al-Dous, Dina Ahram, Somayyeh Abbasi, Eman Abuazab, Hibah Shaath, Wesal Habbab, Khaoula Errafii‬, Yosra Bejaoui, Maryam AlMotawa, Namat Khattab, Yasmin Abu Aqel, Karim E. Shalaby, Amina Al-Ansari, Marios Kambouris, Adel Abouzohri, Iman Ghazal, Mohammed Tolfat, Fouad Alshaban, Hatem El-Shanti, and Omar M. E. Albagha. The genetic landscape of autism spectrum disorder in the middle eastern population. Frontiers in Genetics, Mar 2024. URL: https://doi.org/10.3389/fgene.2024.1363849, doi:10.3389/fgene.2024.1363849. This article has 11 citations and is from a peer-reviewed journal.

19. (alfiya2022c12orf57pathogenicvariants pages 3-4): F. Alfiya, Manna Jose, Soumya V. Chandrasekharan, Soumya Sundaram, Madhusoodanan Urulangodi, Bejoy Thomas, Ashalatha Radhakrishnan, Moinak Banerjee, and Ramshekhar N. Menon. C12orf57 pathogenic variants: a unique cause of developmental encephalopathy in a south indian child. Journal of Genetics, Jun 2022. URL: https://doi.org/10.1007/s12041-022-01371-0, doi:10.1007/s12041-022-01371-0. This article has 5 citations and is from a peer-reviewed journal.

20. (alfiya2022c12orf57pathogenicvariants pages 4-5): F. Alfiya, Manna Jose, Soumya V. Chandrasekharan, Soumya Sundaram, Madhusoodanan Urulangodi, Bejoy Thomas, Ashalatha Radhakrishnan, Moinak Banerjee, and Ramshekhar N. Menon. C12orf57 pathogenic variants: a unique cause of developmental encephalopathy in a south indian child. Journal of Genetics, Jun 2022. URL: https://doi.org/10.1007/s12041-022-01371-0, doi:10.1007/s12041-022-01371-0. This article has 5 citations and is from a peer-reviewed journal.

21. (talisetti2003temtamy‐likesyndromeassociated pages 1-3): Anita Talisetti, Shawnia R. Forrester, David Gregory, Lisa Johnson, Michael C. Schneider, and Virginia E. Kimonis. Temtamy‐like syndrome associated with translocation of 2p24 and 9q32. Clinical Dysmorphology, 12:175–177, Jul 2003. URL: https://doi.org/10.1097/01.mcd.0000072161.33788.56, doi:10.1097/01.mcd.0000072161.33788.56. This article has 20 citations and is from a peer-reviewed journal.

22. (akizu2013wholeexomesequencingidentifies pages 1-2): Naiara Akizu, Nuri M. Shembesh, Tawfeg Ben-Omran, Laila Bastaki, Asma Al-Tawari, Maha S. Zaki, Roshan Koul, Emily Spencer, Rasim Ozgur Rosti, Eric Scott, Elizabeth Nickerson, Stacey Gabriel, Gilberto da Gente, Jiang Li, Matthew A. Deardorff, Laura K. Conlin, Margaret A. Horton, Elaine H. Zackai, Elliott H. Sherr, and Joseph G. Gleeson. Whole-exome sequencing identifies mutated c12orf57 in recessive corpus callosum hypoplasia. American journal of human genetics, 92 3:392-400, Mar 2013. URL: https://doi.org/10.1016/j.ajhg.2013.02.004, doi:10.1016/j.ajhg.2013.02.004. This article has 43 citations and is from a highest quality peer-reviewed journal.

23. (ni2024aninappropriatedecline pages 13-17): Chunyang Ni, Leqian Yu, Barbara Vona, Dayea Park, Yulei Wei, Daniel A Schmitz, Yudong Wei, Yi Ding, Masahiro Sakurai, Emily Ballard, Yan Liu, Ashwani Kumar, Chao Xing, Hyung-Goo Kim, Cumhur Ekmekci, Ehsan Ghayoor Karimiani, Shima Imannezhad, Fatemeh Eghbal, Reza Shervin Badv, Eva Maria Christina Schwaibold, Mohammadreza Dehghani, Mohammad Yahya Vahidi Mehrjardi, Zahra Metanat, Hosein Eslamiyeh, Ebtissal Khouj, Saleh Mohammed Nasser Alhajj, Aziza Chedrawi, César Augusto Pinheiro Ferreira Alves, Henry Houlden, Michael Kruer, Fowzan S. Alkuraya, Can Cenik, Reza Maroofian, Jun Wu, and Michael Buszczak. An inappropriate decline in ribosome levels drives a diverse set of neurodevelopmental disorders. BioRxiv, Jan 2024. URL: https://doi.org/10.1101/2024.01.09.574708, doi:10.1101/2024.01.09.574708. This article has 4 citations.

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25. (akizu2013wholeexomesequencingidentifies pages 7-8): Naiara Akizu, Nuri M. Shembesh, Tawfeg Ben-Omran, Laila Bastaki, Asma Al-Tawari, Maha S. Zaki, Roshan Koul, Emily Spencer, Rasim Ozgur Rosti, Eric Scott, Elizabeth Nickerson, Stacey Gabriel, Gilberto da Gente, Jiang Li, Matthew A. Deardorff, Laura K. Conlin, Margaret A. Horton, Elaine H. Zackai, Elliott H. Sherr, and Joseph G. Gleeson. Whole-exome sequencing identifies mutated c12orf57 in recessive corpus callosum hypoplasia. American journal of human genetics, 92 3:392-400, Mar 2013. URL: https://doi.org/10.1016/j.ajhg.2013.02.004, doi:10.1016/j.ajhg.2013.02.004. This article has 43 citations and is from a highest quality peer-reviewed journal.

26. (marafi2024foundermutationsand pages 4-5): Dana Marafi. Founder mutations and rare disease in the arab world. Disease Models & Mechanisms, Jun 2024. URL: https://doi.org/10.1242/dmm.050715, doi:10.1242/dmm.050715. This article has 18 citations and is from a domain leading peer-reviewed journal.

27. (plassmeyer2023amassivelyparallel pages 21-23): Stephen P. Plassmeyer, Colin P. Florian, Michael J. Kasper, Rebecca Chase, Shayna Mueller, Yating Liu, Kelli McFarland White, Courtney F. Jungers, Slavica Pavlovic Djuranovic, Sergej Djuranovic, and Joseph D. Dougherty. A massively parallel screen of 5′utr mutations identifies variants impacting translation and protein production in neurodevelopmental disorder genes. MedRxiv, Nov 2023. URL: https://doi.org/10.1101/2023.11.02.23297961, doi:10.1101/2023.11.02.23297961. This article has 15 citations.

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29. (wang2020temtamysyndromecaused media b3d8bfd5): Yanqin Wang, Ming Li, Yuanyuan Luo, Xin Zhao, Shuang Liao, Li Jiang, Xiujuan Li, and Min Zhong. Temtamy syndrome caused by a new c12orf57 variant in a chinese boy, including pedigree analysis and literature review. Experimental and therapeutic medicine, 19 1:327-332, Nov 2020. URL: https://doi.org/10.3892/etm.2019.8183, doi:10.3892/etm.2019.8183. This article has 8 citations and is from a peer-reviewed journal.

30. (wang2020temtamysyndromecaused media 805b1c71): Yanqin Wang, Ming Li, Yuanyuan Luo, Xin Zhao, Shuang Liao, Li Jiang, Xiujuan Li, and Min Zhong. Temtamy syndrome caused by a new c12orf57 variant in a chinese boy, including pedigree analysis and literature review. Experimental and therapeutic medicine, 19 1:327-332, Nov 2020. URL: https://doi.org/10.3892/etm.2019.8183, doi:10.3892/etm.2019.8183. This article has 8 citations and is from a peer-reviewed journal.

31. (wang2020temtamysyndromecaused media 21e24220): Yanqin Wang, Ming Li, Yuanyuan Luo, Xin Zhao, Shuang Liao, Li Jiang, Xiujuan Li, and Min Zhong. Temtamy syndrome caused by a new c12orf57 variant in a chinese boy, including pedigree analysis and literature review. Experimental and therapeutic medicine, 19 1:327-332, Nov 2020. URL: https://doi.org/10.3892/etm.2019.8183, doi:10.3892/etm.2019.8183. This article has 8 citations and is from a peer-reviewed journal.

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