Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders. Mutations altering genes involved in the junction between brain cells have been repeatedly associated in ASD. For example, SHANK1, SHANK2 and SHANK3 emerged as one family of genes that are associated with ASD. However, little was known about the number of patients carrying these mutations and the clinical outcome. Here, we performed a new genetic screen of SHANK mutations and these results were analyzed in combination with those of the literature. In summary, SHANK mutations account for ∼1% of patients with ASD and were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. Given the high frequency and impact of SHANK3 mutations in individuals with ASD and intellectual disability—more than 1 in 50—this gene should be screened for mutations in clinical practice.
Vyšlo v časopise: Meta-analysis of Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004580 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004580
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