Genotype-phenotype profile of global ASPH-associated ectopia lentis and clinical findings from a Chinese cohort.
Gene
; 925: 148600, 2024 Oct 20.
Article
in En
| MEDLINE
| ID: mdl-38788814
ABSTRACT
BACKGROUND:
Traboulsi syndrome is an under-recognized syndromic form of ectopia lentis (EL) caused by the aspartate beta-Hydroxylase (ASPH) variant. The genotype-phenotype profile of ASPH-associated disease is poorly understood due to the rarity of the condition.METHODS:
We conducted targeted next-generation sequencing and bioinformatics analysis to identify potentially pathogenic ASPH variants in the cohort. Furthermore, we characterized the expression pattern of ASPH and major components of the zonules using single-cell RNA-sequencing (scRNA-seq) and evaluated the genotype-phenotype correlations by combining our data and those from the literature.RESULTS:
We identified a novel missense variant c.2075G > A (p.G692D) and a recurrent nonsense variant c.1126C > G (p.R376*) of ASPH in two pedigrees from a Chinese cohort of EL. Both probands were 5-year-old boys with canonical facial dysmorphisms and bilateral anteriorly-dislocated lenses. Other ocular comorbidities included microspherophakia, shallow anterior chamber, and narrow chamber angel. No cardiac involvements or filtering blebs were identified. The single-cell expression atlas of ciliary epithelium demonstrated the coexpression of ASPH with FBN1, FBN2, and LTBP2 in the non-pigmented ciliary epithelium cells. Furthermore, molecular modeling simulation of p.G692D revealed increased affinity to the cb EGF-like domain and a subsequent destabilized calcium-binding motif. The genotype-phenotype analysis demonstrated that patients with cardiac involvements all harbored biallelic truncation variants.CONCLUSIONS:
The data from this study provide new insights into the genotype-phenotype profile of ASPH-associated disease and implicate the potential role of ASPH in the pathogenesis of EL.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pedigree
/
Ectopia Lentis
/
Genetic Association Studies
Limits:
Child, preschool
/
Female
/
Humans
/
Male
Country/Region as subject:
Asia
Language:
En
Journal:
Gene
Year:
2024
Document type:
Article
Country of publication: