Titel: First description of inheritance of a postzygotic OPA1 mosaic variant
ID: P-ClinG-034
Art: Postertalk
Redezeit: 2 min
Session: Poster Session
ClinG 2

Referent: Svenja Alter (Freiburg/DE)

Abstract - Text


Optic atrophy 1 (MIM #165500) is caused by pathogenic variants in the gene OPA1 (OPA1 MI-TOCHONDRIAL DYNAMIN-LIKE GTPase, MIM *605290) and is inherited in an autosomal dominant manner. We describe a 6-year-old male patient with a severe early onset manifestation of optic atrophy, whose parents are subjectively asymptomatic. OPA1 mutation analysis revealed the heterozygous missense variant NM_015560.3:c.806C>T, p.(Ser269Phe) in the patient. The father did not carry the variant, whereas in the mother we detected a low-grade mosaicism of the variant c.806C>T of approximately 10 %. To determine the degree of mosaicism precisely, we analyzed the DNA of the mother obtained from different tissues i) peripheral blood, ii) oral mucosa and iii) skin by next-generation sequencing (NGS). We detected the variant with a mosaic of 15.3 % variant allele frequency (VAF) in peripheral blood, 18.4 % in oral mucosa and 10.0 % in skin. In line with this, ophthalmological investigation of the mother showed subclinical manifestation of Optic atrophy 1. To our knowledge, this is the first report of an OPA1 postzygotic mosaic in a parent that was inherited to offspring.