First Description of Inheritance of a Postzygotic OPA1 Mosaic Variant

Svenja Alter; Navid Farassat; Sebastian Küchlin; Wolf A Lagrèze; Judith Fischer

doi:10.3390/genes13030478

First Description of Inheritance of a Postzygotic OPA1 Mosaic Variant

Genes (Basel). 2022 Mar 8;13(3):478. doi: 10.3390/genes13030478.

Authors

Svenja Alter¹, Navid Farassat², Sebastian Küchlin², Wolf A Lagrèze², Judith Fischer¹

Affiliations

¹ Institute of Human Genetics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
² Eye Center, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.

Abstract

Optic atrophy 1 (MIM #165500) is caused by pathogenic variants in the gene OPA1 (OPA1 MITOCHONDRIAL DYNAMIN-LIKE GTPase, MIM *605290) and is inherited in an autosomal dominant manner. We describe a 6-year-old male patient with severe early onset manifestation of optic atrophy, whose parents are subjectively asymptomatic. OPA1-sequence analysis revealed the heterozygous missense variant NM_015560.3:c.806C>T, p.(Ser269Phe) in the patient. Segregation analysis of the parents showed that the mother carried a low-grade postzygotic mosaic of this variant, which apparently also involves germline cells. In line with this, ophthalmological investigation of the mother showed subclinical manifestation of optic atrophy 1. This is the first report of an OPA1 postzygotic mosaic that was inherited to offspring.

Keywords: ADOA; OPA1; optic atrophy; postzygotic mosaic.

Publication types

Case Reports

MeSH terms

Child
Dynamins / genetics
GTP Phosphohydrolases / genetics
Humans
Male
Mutation, Missense
Optic Atrophy* / pathology
Optic Atrophy, Autosomal Dominant* / genetics
Optic Atrophy, Autosomal Dominant* / pathology

Substances

GTP Phosphohydrolases
OPA1 protein, human
Dynamins