Defective Sec61α1 underlies a novel cause of autosomal dominant severe congenital neutropenia.

ABSTRACT:

Background

The molecular cause of severe congenital neutropenia (SCN) is unknown in 30% to 50% of patients. SEC61A1 encodes the α-subunit of the Sec61 complex, which governs endoplasmic reticulum protein transport and passive calcium leakage. Recently, mutations in SEC61A1 were reported to be pathogenic in common variable immunodeficiency and glomerulocystic kidney disease.

Objective

Our aim was to expand the spectrum of SEC61A1-mediated disease to include autosomal dominant SCN.

Methods

Whole exome sequencing findings were validated, and reported mutations were compared by Western blotting, Ca2⁺ flux assays, differentiation of transduced HL-60 cells, in vitro differentiation of primary CD34 cells, quantitative PCR for unfolded protein response (UPR) genes,

SUBMITTER: Van Nieuwenhove E 

PROVIDER: S-EPMC7649975 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature