Phenotypic spectrum associated with de novo mutations in QRICH1 gene.

Rare de novo mutations represent a significant cause of idiopathic developmental delay (DD). The use of next-generation sequencing (NGS) has boosted the identification of de novo mutations in an increasing number of novel genes. Here we present 3 unrelated children with de novo loss-of-function (LoF) mutations in QRICH1, diagnosed through trio-based exome sequencing. QRICH1 encodes the glutamine-rich protein 1, which contains 1 caspase activation recruitment domain and is likely to be involved in apoptosis and inflammation. All 3 children had speech delay, learning difficulties, a prominent nose and a thin upper lip. In addition, 2 of them had mildly raised creatine kinase (CK) and 1 of them had autism. Despite their small number, the patients had a relatively consistent pattern of clinical features suggesting the presence of a QRICH1-associated phenotype. LoF mutations in QRICH1 are suggested as a novel cause of DD.