Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Mol Genet Genomic Med ; 8(3): e1123, 2020 03.
Article in English | MEDLINE | ID: mdl-31968401

ABSTRACT

BACKGROUND: Inherited retinal dystrophies (IRDs) are characterized by extreme genetic and clinical heterogeneity. There are many genes that are known to cause IRD which makes the identification of the underlying genetic causes quite challenging. And in view of the emergence of therapeutic options, it is essential to combine molecular and clinical data to correctly diagnose IRD patients. In this study, we aimed to identify the disease-causing variants (DCVs) in four consanguineous Jordanian families with IRDs and describe genotype-phenotype correlations. METHODS: Exome sequencing (ES) was employed on the proband patients of each family, followed by segregation analysis of candidate variants in affected and unaffected family members by Sanger sequencing. Simulation analysis was done on one novel CLRN1 variant to characterize its effect on mRNA processing. Clinical evaluation included history, slit-lamp biomicroscopy, and indirect ophthalmoscopy. RESULTS: We identified two novel variants in CLRN1 [(c.433+1G>A) and (c.323T>C, p.Leu108Pro)], and two recurrent variants in ABCA4 [(c.1648G>A, p.Gly550Arg) and (c.5460+1G>A)]. Two families with the same DCV were found to have different phenotypes and another family was shown to have sector RP. Moreover, simulation analysis for the CLRN1 splice donor variant (c.433+1G>A) showed that the variant might affect mRNA processing resulting in the formation of an abnormal receptor. Also, a family that was previously diagnosed with nonsyndromic RP was found to have Usher syndrome based on their genetic assessment and audiometry. CONCLUSION: Our findings extend the spectrum of CLRN1- and ABCA4-associated IRDs and describe new phenotypes for these genes. We also highlighted the importance of combining molecular and clinical data to correctly diagnose IRDs and the utility of simulation analysis to predict the effect of splice donor variants on protein formation and function.


Subject(s)
ATP-Binding Cassette Transporters/genetics , Membrane Proteins/genetics , Mutation , Retinal Dystrophies/genetics , Adult , Child , Exome , Female , Humans , Male , Membrane Proteins/chemistry , Middle Aged , Pedigree , Phenotype , RNA Splicing , Retinal Dystrophies/pathology
2.
Can J Ophthalmol ; 54(1): 51-59, 2019 02.
Article in English | MEDLINE | ID: mdl-30851774

ABSTRACT

OBJECTIVE: To identify the disease-causing variants in 2 families with autosomal recessive inherited retinal dystrophies (IRDs) and to characterize phenotypic variability across the affected family members. DESIGN: Exome sequencing and ophthalmic clinical examination study. PARTICIPANTS: Six members from 2 consanguineous Jordanian families with IRD. METHODS: Ophthalmic examinations and whole-exome sequencing (WES) were performed to identify IRD-causing variants in affected individuals from each family, followed by segregation analysis of candidate variants in affected and unaffected family members by Sanger sequencing. RESULTS: We identified 2 different homozygous deletion variants in CERKL in each family: a novel pathogenic variant, c.450_451delAT, and a known variant, c.1187_1188delTG. Both variants co-segregated with the disease in all affected family members. The resulting phenotypes further supported that CERKL is associated with cone-rod dystrophy (CRD) rather than retinitis pigmentosa (RP), as originally established. CONCLUSION: Our study expands the genotypic spectra of CERKL variants, providing insights into the relevant pathogenesis of RP/CRD. We also confirm that the WES approach is a valuable tool for the molecular diagnosis of retinopathies.


Subject(s)
Consanguinity , DNA/genetics , Mutation , Phosphotransferases (Alcohol Group Acceptor)/genetics , Retinal Dystrophies/genetics , Adolescent , Adult , DNA Mutational Analysis , Exome , Female , Genotype , Humans , Jordan , Male , Middle Aged , Pedigree , Phenotype , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Retinal Dystrophies/congenital , Retinal Dystrophies/metabolism , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...