RESUMEN
UNLABELLED: We report on an 8-year-old boy with autism spectrum disorder (ASD), speech delay, behavioural problems, disturbed sleep and macrosomia including macrocephaly carrying a microdeletion that contains the entire NCAM2 gene and no other functional genes. Other family members with the microdeletion show a large skull circumference but do not exhibit any symptoms of autism spectrum disorder. Among many ASD-candidate genes, NCAM2 has been assumed to play a pivotal role in the development of ASD because of its function in the outgrowth and bundling of neurites. Our reported case raises the questions whether the NCAM2-deletion is the true cause of the ASD or only a risk factor and whether there might be any connection in NCAM2 with skull-size KEY WORDS: autism spectrum disorder, macrocephaly, neural cell adhesion molecule 2 protein (NCAM2), array comparative genomic hybridization (microarray).
Asunto(s)
Trastorno del Espectro Autista/genética , Trastorno Autístico/genética , Megalencefalia/genética , Molécula L1 de Adhesión de Célula Nerviosa/genética , Trastorno del Espectro Autista/fisiopatología , Trastorno Autístico/fisiopatología , Niño , Deleción Cromosómica , Hibridación Genómica Comparativa , Facies , Predisposición Genética a la Enfermedad , Humanos , Trastornos del Desarrollo del Lenguaje/genética , Trastornos del Desarrollo del Lenguaje/fisiopatología , Masculino , Megalencefalia/fisiopatología , Moléculas de Adhesión de Célula Nerviosa , Factores de RiesgoRESUMEN
CHARGE syndrome is an autosomal dominant inherited multiple malformation disorder typically characterized by coloboma, choanal atresia, hypoplastic semicircular canal, cranial nerve defects, cardiovascular malformations and ear abnormalities. Mutations in the chromodomain helicase DNA-binding protein 7 (CHD7) gene are the major cause of CHARGE syndrome. Mutation analysis was performed in 18 patients with firm or tentative clinical diagnosis of CHARGE syndrome. In this study eight mutations distributed across the gene were found. Five novel mutations - one missense (c.2936T > C), one nonsense (c.8093C > A) and three frameshift mutations (c.804_805insAT, c.1757_1770del14, c.1793delA) - were identified. As far as familial data were available these mutations were found to have arisen de novo. Comparison of the clinical features of patients with the same mutation demonstrates that expression of the phenotype is highly variable. The mutation detection rate in this study was 44.4% in patients with a clinically established or suspected diagnosis of CHARGE syndrome.