A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP

• Published in: Nature genetics Vol. 46; no. 4; pp. 380 - 384
• Main Authors: Helsmoortel, Céline, Vulto-van Silfhout, Anneke T, Coe, Bradley P, Vandeweyer, Geert, Rooms, Liesbeth, van den Ende, Jenneke, Schuurs-Hoeijmakers, Janneke H M, Marcelis, Carlo L, Willemsen, Marjolein H, Vissers, Lisenka E L M, Yntema, Helger G, Bakshi, Madhura, Wilson, Meredith, Witherspoon, Kali T, Malmgren, Helena, Nordgren, Ann, Annerén, Göran, Fichera, Marco, Bosco, Paolo, Romano, Corrado, de Vries, Bert B A, Kleefstra, Tjitske, Kooy, R Frank, Eichler, Evan E, Van der Aa, Nathalie
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2014; Nature Publishing Group
• Subjects: 45/23; 45/77; 45/88; 45/90; 631/208/2489; 692/308/2056; 692/699/375/366; Abnormalities, Multiple - genetics; Agriculture; Amino acids; Animal Genetics and Genomics; Autism; Base Sequence; Biomedicine; Cancer Research; Child Development Disorders, Pervasive - genetics; Chromosomal Proteins, Non-Histone - genetics; Chromosome aberrations; Chromosomes; Codon, Nonsense - genetics; Comorbidity; Confidence intervals; Deoxyribonucleic acid; DNA; Exome - genetics; Frameshift Mutation - genetics; Gene Components; Gene Function; Gene mutations; Genes; Genetic aspects; Heterogeneity; Homeodomain Proteins - genetics; Human Genetics; Humans; Identification and classification; letter; Medical research; Molecular Sequence Data; Mutation; Nerve Tissue Proteins - genetics; Patients; Proteins; Real-Time Polymerase Chain Reaction; Recruitment; Sequence Analysis, DNA; Studies; Transcription factors; Transcription Factors - genetics
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.2899

Frank Kooy, Nathalie Van der Aa and colleagues report that de novo mutations in ADNP cause a syndrome characterized by autism, intellectual disability and facial dysmorphisms. ADNP encodes a transcription factor that interacts with components of the SWI/SNF chromatin remodeling complex. Despite the high heritability of autism spectrum disorders (ASD), characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests or activities 1 , a genetic diagnosis can be established in only a minority of patients. Known genetic causes include chromosomal aberrations, such as the duplication of the 15q11-13 region, and monogenic causes, as in Rett and fragile-X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. Even with the recent developments in next-generation sequencing, for the large majority of cases no molecular diagnosis can be established 2 , 3 , 4 , 5 , 6 , 7 . Here, we report ten patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP , a transcription factor involved in the SWI/SNF remodeling complex. We estimate this gene to be mutated in at least 0.17% of ASD cases, making it one of the most frequent ASD-associated genes known to date.