Pathogenic variants in RNPC3 are associated with hypopituitarism and primary ovarian insufficiency.

ABSTRACT:

Purpose

We aimed to investigate the molecular basis underlying a novel phenotype including hypopituitarism associated with primary ovarian insufficiency.

Methods

We used next-generation sequencing to identify variants in all pedigrees. Expression of Rnpc3/RNPC3 was analyzed by in situ hybridization on murine/human embryonic sections. CRISPR/Cas9 was used to generate mice carrying the p.Leu483Phe pathogenic variant in the conserved murine Rnpc3 RRM2 domain.

Results

We described 15 patients from 9 pedigrees with biallelic pathogenic variants in RNPC3, encoding a specific protein component of the minor spliceosome, which is associated with a hypopituitary phenotype, including severe growth hormone (GH) deficiency, hypoprolactinemia, variable thyrotropin (also known as th

SUBMITTER: Akin L 

PROVIDER: S-EPMC7612377 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature