METAP1 mutation is a novel candidate for autosomal recessive intellectual disability.

TitleMETAP1 mutation is a novel candidate for autosomal recessive intellectual disability.
Publication TypeJournal Article
Year of Publication2020
AuthorsÇağlayan, AOkay, Aktar, F, Bilguvar, K, Baranoski, JF, Akgümüş, GTuğce, Harmanci, ASerin, Erson-Omay, EZeynep, Yasuno, K, Caksen, H, Günel, M
JournalJ Hum Genet
Date Published2020 Aug 06
ISSN1435-232X
Abstract

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.

DOI10.1038/s10038-020-0820-0
Alternate JournalJ. Hum. Genet.
PubMed ID32764695
Grant ListUM1 HG006504 / HG / NHGRI NIH HHS / United States
U54HG006504 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
U24HG008956 / / U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) /