Alternative splicing expands the clinical spectrum of NDUFS6-related mitochondrial disorders.

ABSTRACT:

Purpose

We describe 3 families with Charcot-Marie-Tooth neuropathy (CMT), harboring a homozygous NDUFS6 NM_004553.6:c.309+5G>A variant previously linked to fatal Leigh syndrome. We aimed to characterize clinically and molecularly the newly identified patients and understand the mechanism underlying their milder phenotype.

Methods

The patients underwent extensive clinical examinations. Exome sequencing was done in 4 affected individuals. The functional effect of the c.309+5G>A variant was investigated in patient-derived EBV-transformed lymphoblasts at the complementary DNA, protein, and mitochondrial level. Alternative splicing was evaluated using complementary DNA long-read sequencing.

Results

All patients presented with early-onset, slowly progressive axonal CMT, and

SUBMITTER: Armirola-Ricaurte C 

PROVIDER: S-EPMC11180951 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature