Three brothers with a nonsense mutation in caused by parental germline mosaicism.

Mutations in , encoding a member of the MYST family of histone acetyl-transferases, were recently reported in patients with a neurodevelopmental disorder (OMIM: #616268, autosomal dominant mental retardation-32). In this report, we describe three siblings with intellectual disability (ID) or global developmental delay and a heterozygous nonsense mutation, i.e., c.3070C>T (p.R1024*, ENST00000406337; chr8:41795056G>A on hg19). This mutation was identified by whole-exome sequencing of all three siblings but not in a healthy sibling. The mutation was not detected in the peripheral blood of their parents, suggesting the existence of parental germline mosaicism. The primary symptoms of our patients included severe to profound ID or global developmental delay, including speech delay with craniofacial dysmorphism; these symptoms are consistent with symptoms previously described for patients with mutations. Although several features are common among patients with mutations, the features are relatively nonspecific, making it difficult to establish a clinical entity based on clinical findings alone. To the best of our knowledge, this is the first report of cases with a mutation in an Asian population and these cases represent the first reported instances of germline mosaicism of this disease.