WAC loss-of-function mutations cause a recognisable syndrome characterised by dysmorphic features, developmental delay and hypotonia and recapitulate 10p11.23 microdeletion syndrome

Mutations in the WAC gene have been recently reported in large screening cohorts of patients with intellectual disability or autism. We used whole exome sequencing to evaluate 6 patients with developmental delay, hypotonia, behavioral problems, constipation/feeding difficulties and common dysmorphic features including broad/prominent forehead, synophrys and/or bushy eyebrows, depressed nasal bridge and bulbous nasal tip. We identified 5 heterozygous loss-of-function WAC mutations; one mutation was found in two siblings but not detected in their healthy parents, strongly suggesting germline mosaicism. Our data highly suggest that WAC haploinsufficiency is responsible for the neurocognitive phenotype and facial dysmorphism associated with deletions encompassing 10p11.23 (By Marwan Shinawi, M.D., http://jmg.bmj.com/content/early/2015/08/11/jmedgenet-2015-103069 )