Co-existence of 2 clinically significant variants causing disorders of somatic mosaicism.

ABSTRACT:

Purpose

Disorders of somatic mosaicism (DoSM) are a heterogeneous group of conditions caused by postzygotic variants in genes within the PI3K/AKT/mTOR and RAS/MAPK signaling pathway. The co-existence of 2 activating variants in this disease group is extremely rare.

Methods

A deep sequencing next-generation sequencing assay for the molecular diagnosis of DoSM was run on 936 individuals with DoSM.

Results

A single pathogenic or likely pathogenic (P/LP) variant was identified in 584 of 617 (94.8%) positive cases; 33 of 617 (5.2%) cases carried 2 P/LP variants. Of these 33 cases, 22 carried 2 P/LP variants in the same gene, including 8 associated with a loss-of-function disease mechanism and 14 associated with a gain-of-function disease mechanism. Eleven cases had P/LP va

SUBMITTER: Cao Y 

PROVIDER: S-EPMC11613713 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature