Sara Banihashemi, Maryam Tahmasebi-Birgani, J. Mohammadiasl
Jan 21, 2020
European journal of medical genetics
Intellectual disability (ID) is characterized by significant deficits in adaptive behaviors and cognitive functioning. The involvement of both genetic and environmental factors in pathogenesis of the ID, makes the diagnosis of the disease more complicated. Nowadays, the entrance of next generation sequencing (NGS) approaches has facilitated the discovery of causative genes in this genetically heterogeneous disease. Here, we report a novel nonsense mutation (c.115 C > T, p.Gln39X) of INPP4A gene in a family with inherited ID using whole exome sequencing (WES). The mutation was completely co-segregated with disease phenotype in all affected members, and unaffected members of family were either homozygous or heterozygous. In silico analysis predicted the c.115 C > T; p.Gln39X as probably pathogenic variant. It seems that mutated transcript would degrade through nonsense-mediated decay (NMD) or potentially form strongly truncated protein lacking functionally important domain like C2A_copine. The INPP4A is an important neuroprotective protein which is preferentially detected in brain. The variant c.115C > T; p.Gln39X is the third reported mutation of INPP4A gene in neurological diseases. Such variants further expand the mutation spectrum in INPP4A and substantiate its role in the pathogenesis of ID. However, more experimental data are needed for considering these mutations in genetic counseling.