The ASXL1 mutation p.Gly646Trpfs*12 found in a Turkish boy with Bohring-Opitz syndrome

Abstract

Bohring‐Opitz syndrome (BOS, MIM #605039) is a rare and severe disease characterized mainly by intrauterine growth retardation, feeding difficulties, severe to profound developmental delay, nonspecific brain abnormalities, microcephaly, flexion at the elbows with ulnar deviation and flexion of the wrists and metacarpophalangeal joints (known as BOS posture) and distinctive facial features.1 Heterozygous ASXL1 truncating mutations have been identified as the main cause of BOS.1, 2 A recent publication 3 called the attention to the fact that mutations associated with BOS are also present in the ExAC (Exome Aggregation Consortium) database.4 As ASXL1 is one of the genes most commonly mutated during hematopoietic clonal expansion of cells, the authors hypothesized that the presence of this mutation in public databases could be due to somatic mosaicism, and they could confirm the hypothesis by manual examination of the ExAC WES reads.