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

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

Nature genetics (2014-02-18)

Céline Helsmoortel, Anneke T Vulto-van Silfhout, Bradley P Coe, Geert Vandeweyer, Liesbeth Rooms, Jenneke van den Ende, Janneke H M Schuurs-Hoeijmakers, Carlo L Marcelis, Marjolein H Willemsen, Lisenka E L M Vissers, Helger G Yntema, Madhura Bakshi, Meredith Wilson, Kali T Witherspoon, Helena Malmgren, Ann Nordgren, Göran Annerén, Marco Fichera, Paolo Bosco, Corrado Romano, Bert B A de Vries, Tjitske Kleefstra, R Frank Kooy, Evan E Eichler, Nathalie Van der Aa

PMID24531329

ZUSAMMENFASSUNG

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, 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. 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.