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Novel heterozygous OPA3 variant in a family with congenital cataracts, sensorineural hearing loss and neuropathy, without optic atrophy and comparison of pathogenic and population variants.
- Source :
-
American journal of medical genetics. Part A [Am J Med Genet A] 2025 Jan; Vol. 197 (1), pp. e63846. Date of Electronic Publication: 2024 Aug 21. - Publication Year :
- 2025
-
Abstract
- Heterozygous mutations in the OPA3 gene are associated with autosomal dominant optic atrophy-3 (OPA3), whereas biallelic mutations cause autosomal recessive 3-methylglutaconic aciduria type III. To date, all cases with pathogenic variants in the gene OPA3 have presented with optic atrophy. We report a large family with congenital cataracts, hearing loss and neuropathy, with a likely pathogenic novel missense variant in OPA3, c.30G>C; p.(Lys10Asn) that segregates with disease in the family pedigree. The family's clinical presentation has significant phenotypic overlap with previously reported cases of OPA3, except for a notable lack of optic atrophy. The analysis of all known disease-associated variants in OPA3 revealed an enrichment in missense variants in patients with OPA3 phenotype compared with loss-of-function variants, which are more likely to be observed in individuals with 3-methylglutaconic aciduria type III, supporting different mechanisms of disease. This case broadens the clinical and genetic spectrum associated with OPA3 mutations and highlights that optic atrophy is not an obligate feature of OPA3-related disorders.<br /> (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)
- Subjects :
- Humans
Female
Male
Optic Atrophy genetics
Optic Atrophy pathology
Phenotype
Mutation genetics
Mutation, Missense genetics
Adult
Child
GTP Phosphohydrolases genetics
Proteins
Cataract genetics
Cataract pathology
Cataract congenital
Pedigree
Hearing Loss, Sensorineural genetics
Hearing Loss, Sensorineural pathology
Heterozygote
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4833
- Volume :
- 197
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of medical genetics. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 39166438
- Full Text :
- https://doi.org/10.1002/ajmg.a.63846