Fatal perinatal mitochondrial cardiac failure caused by recurrent de novo duplications in the ATAD3 locus.

ABSTRACT:

Background

In about half of all patients with a suspected monogenic disease, genomic investigations fail to identify the diagnosis. A contributing factor is the difficulty with repetitive regions of the genome, such as those generated by segmental duplications. The ATAD3 locus is one such region, in which recessive deletions and dominant duplications have recently been reported to cause lethal perinatal mitochondrial diseases characterized by pontocerebellar hypoplasia or cardiomyopathy, respectively.

Methods

Whole exome, whole genome and long-read DNA sequencing techniques combined with studies of RNA and quantitative proteomics were used to investigate 17 subjects from 16 unrelated families with suspected mitochondrial disease.

Findings

We report six differen

SUBMITTER: Frazier AE 

PROVIDER: S-EPMC7875323 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature