Mutations in the m-AAA proteases AFG3L2 and SPG7 are causing isolated dominant optic atrophy.

ABSTRACT:

Objective

To improve the genetic diagnosis of dominant optic atrophy (DOA), the most frequently inherited optic nerve disease, and infer genotype-phenotype correlations.

Methods

Exonic sequences of 22 genes were screened by new-generation sequencing in patients with DOA who were investigated for ophthalmology, neurology, and brain MRI.

Results

We identified 7 and 8 new heterozygous pathogenic variants in SPG7 and AFG3L2. Both genes encode for mitochondrial matricial AAA (m-AAA) proteases, initially involved in recessive hereditary spastic paraplegia type 7 (HSP7) and dominant spinocerebellar ataxia 28 (SCA28), respectively. Notably, variants in AFG3L2 that result in DOA are located in different domains to those reported in SCA28, which likely expl

SUBMITTER: Charif M 

PROVIDER: S-EPMC7251510 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature