Maternal mosaicism in SSBP1 causing optic atrophy with retinal degeneration: implications for genetic counseling

Background: Optic atrophy-13 with retinal and foveal abnormalities (OPA13) (MIM #165510) is a mitochondrial disease in which apparent bilateral optic atrophy is present and sometimes followed by retinal pigmentary changes or photoreceptors degeneration. OPA13 is caused by heterozygous mutation in the SSBP1 gene, associated with variable mitochondrial dysfunctions. Results: We have previously reported a 16-year-old Taiwanese male diagnosed with OPA13 and SSBP1 variant c.320G>A (p.Arg107Gln) was identified by whole exon sequence (WES). This variant was assumed to be de novo since his parents were clinically unaffected. However, WES and Sanger sequencing further revealed the proband’s unaffected mother carrying the same SSBP1 variant with a 13% variant allele frequency (VAF) in her peripheral blood. That finding strongly indicates the maternal gonosomal mosaicism contributing to OPA13, which has not been reported before. Conclusions: In summary, we described the first case of OPA13 caused by maternal gonosomal mosaicism in SSBP1. Parental mosaicism could be a serious issue in OPA13 diagnosis, and appropriate genetic counseling should be considered.