Impaired EIF2S3 function associated with a novel phenotype of X-linked hypopituitarism with glucose dysregulation.

ABSTRACT:

Background

The heterotrimeric GTP-binding protein eIF2 forms a ternary complex with initiator methionyl-tRNA and recruits it to the 40S ribosomal subunit for start codon selection and thereby initiates protein synthesis. Mutations in EIF2S3, encoding the eIF2γ subunit, are associated with severe intellectual disability and microcephaly, usually as part of MEHMO syndrome.

Methods

Exome sequencing of the X chromosome was performed on three related males with normal head circumferences and mild learning difficulties, hypopituitarism (GH and TSH deficiencies), and an unusual form of glucose dysregulation. In situ hybridisation on human embryonic tissue, EIF2S3-knockdown studies in a human pancreatic cell line, and yeast assays on the mutated corresponding eIF2γ protein, were per

SUBMITTER: Gregory LC 

PROVIDER: S-EPMC6492072 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature