First Description of Inheritance of a Postzygotic OPA1 Mosaic Variant

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.