Most cited article - PubMed ID 28576131
Analysis of 31-year-old patient with SYNGAP1 gene defect points to importance of variants in broader splice regions and reveals developmental trajectory of SYNGAP1-associated phenotype: case report
BACKGROUND: Intellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic variants in a specific gene are found only in a small number of patients, and difficulties arise in the definition of prevailing genotype and characteristic phenotype associated with that gene. One of such very rare disorders is autosomal recessive ID type 66 (OMIM #618221) caused by defects in C12orf4. Up to now, six families have been reported with mostly truncating variants. The spectrum of the clinical phenotype was not emphasized in previous reports, and detailed phenotype was not always available from previous patients, especially from large cohort studies. METHODS: Exome sequencing was performed in a consanguineous Armenian family with two affected adult brothers. RESULTS: The patients carry a novel homozygous nonsense C12orf4 variant. The integration of previous data and phenotyping of the brothers indicate that the clinical picture of C12orf4 defects involves hypotonia in infancy, rather severe ID, speech impairment, and behavioral problems such as aggressiveness, unstable mood, and autistic features. Several other symptoms are more variable and less consistent. CONCLUSION: This rather nonsyndromic and nonspecific clinical picture implies that additional patients with C12orf4 defects will likely continue to be identified using the "genotype-first" approach, rather than based on clinical assessment. The phenotype needs further delineation in future reports.
- Keywords
- C12orf4, consanguinity, exome sequencing, intellectual disability,
- MeSH
- Alleles MeSH
- Adult MeSH
- Facies MeSH
- Phenotype * MeSH
- Genes, Recessive * MeSH
- Homozygote MeSH
- Intracellular Signaling Peptides and Proteins genetics MeSH
- Polymorphism, Single Nucleotide MeSH
- Humans MeSH
- Intellectual Disability diagnosis genetics MeSH
- DNA Mutational Analysis MeSH
- Consanguinity * MeSH
- Child, Preschool MeSH
- Pedigree MeSH
- Exome Sequencing MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Armenia epidemiology MeSH
- Names of Substances
- C12orf4 protein, human MeSH Browser
- Intracellular Signaling Peptides and Proteins MeSH
