Journal Article

METAP1 mutation is a novel candidate for autosomal recessive intellectual disability

Aktar, Fesih, Akgumus, Gozde Tugce, Bilguvar, Kaya, Caksen, Huseyin, Harmanci, Akdes Serin, Gunel, Murat, Caglayan, Ahmet Okay, Baranoski, Jacob F., Erson-Omay, Emine Zeynep, Yasuno, Katsuhito

2021

Overview

Intellectual disability (ID) is a genetic and clinically heterogeneous common disease and underlying molecular pathogenesis can frequently not be identified by whole-exome/genome testing. Here, we report four siblings born to a consanguineous union who presented with intellectual disability and discuss the METAP1 pathway as a novel etiology of ID. Genomic analyses demonstrated that patients harbor a novel homozygous nonsense mutation in the gene METAP1. METAP1 codes for methionine aminopeptidase 1 (MetAP1) which oversees the co-translational excision of the first methionine remnants in eukaryotes. The loss-of-function mutations to this gene may result in a defect in the translation of many essential proteins within a cell. Improper neuronal function resulting from this loss of essential proteins could lead to neurologic impairment and ID.

• Publisher: Nature Publishing Group
• Subject: Aminopeptidase / Etiology / Genomes / Genomic analysis / Intellectual disabilities / Methionine / Mutation / Nonsense mutation