Variants in the WDR45 Gene Within the OPA-2 Locus Associate With Isolated X-Linked Optic Atrophy.
Invest Ophthalmol Vis Sci
; 64(13): 17, 2023 10 03.
Article
em En
| MEDLINE
| ID: mdl-37819743
ABSTRACT
Purpose:
To describe clinical and molecular findings of two families with X-linked optic atrophy and present two new pathogenic variants in the WDR45 gene.Methods:
Case series and molecular analysis of two families of Jewish Ashkenazi descent with early onset bilateral optic atrophy. Whole-exome sequencing (WES) and bioinformatic analysis were performed, followed by Sanger sequencing and segregation analysis.Results:
In both families, male siblings (three in family 1, two in family 2) had early-onset isolated bilateral optic atrophy. The sibling's healthy mother (and in the second family also one healthy sister) had a mild presentation, suggesting a carrier state and an X-linked inheritance pattern. All participants were otherwise healthy, apart from mild learning disabilities and autism spectrum disorder in two siblings of the second family. Variants in known optic atrophy genes were excluded. Analysis revealed a point variant in the WDR45 gene-a missense variant in the first family, NM_001029896.2c.107C>A; NP_001025067.1p.Pro36His (variant ID 1704205), and a splice site variant in the second family, NM_001029896.2c.236-1G>T; NP_009006.2p.Val80Leu (variant ID 1704204), located on Xp11.23 (OPA2 locus). Both variants are novel and predicted as pathogenic. In both families, the variant was seen with full segregation with the disease, occurring in all affected male participants and in one allele of the carrier females, as well as none of the healthy participants.Conclusions:
Among two families with isolated X-linked optic atrophy, molecular analysis revealed novel variants in the WDR45 gene in full segregation with the disease. This gene resides within the OPA2 locus, previously described to associate with X-linked optic atrophy. Taken together, these findings suggest that certain pathogenic variants in the WDR45 gene are associated with isolated X-linked optic atrophy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Atrofia Óptica
/
Doenças Genéticas Ligadas ao Cromossomo X
/
Transtorno do Espectro Autista
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Israel