Plasma cell deficiency in human subjects with heterozygous mutations in Sec61 translocon alpha 1 subunit (SEC61A1).

ABSTRACT:

Background

Primary antibody deficiencies (PADs) are the most frequent primary immunodeficiencies in human subjects. The genetic causes of PADs are largely unknown. Sec61 translocon alpha 1 subunit (SEC61A1) is the major subunit of the Sec61 complex, which is the main polypeptide-conducting channel in the endoplasmic reticulum membrane. SEC61A1 is a target gene of spliced X-box binding protein 1 and strongly induced during plasma cell (PC) differentiation.

Objective

We identified a novel genetic defect and studied its pathologic mechanism in 11 patients from 2 unrelated families with PADs.

Methods

Whole-exome and targeted sequencing were conducted to identify novel genetic mutations. Functional studies were carried out ex vivo in primary cells of patients and in vitro

SUBMITTER: Schubert D 

PROVIDER: S-EPMC5797495 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature