Objective: This study aims to clarify the association between keratoconus (KC) and potential pathogenic genetic variants in a three-generation South Indian family.
Methods: In the present study, a three-generation KC family, which comprised 10 affected patients and nine unaffected individuals, was recruited. The family history and necessary ophthalmological exams, such as visual acuity and slit-lamp, were performed for all participants. Genomic DNA was extracted from peripheral blood leukocytes, and whole exome sequencing (WES) was performed using the genomic DNA of the proband (III:4) and two other family members (III:2, III:3). The acceptor-splice-site mutation was validated and verified using polymerase chain reaction (PCR) and Sanger sequencing. Gene functions and pathways associated with the identified mutations were subjected to analysis.
Results: A novel acceptor-splice-site mutation IVS50-4C > G was found in the 10 affected individuals in the three-generation KC family, but this was not found in any of the unaffected family members or unrelated healthy individuals. Gene functional analysis using the SpliceMan and ExonScan software predicted that the splice-site mutation was potentially associated with KC pathogenesis. This mutation might affect the assembly of the collagen triple helix.
Conclusion: The present study confirmed the association between the gene and KC and identified a novel acceptor-splice-site mutation (IVS50-4C > G) in intron 50, which may affect the splicing of the adjacent exon 50.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854226 | PMC |
| http://dx.doi.org/10.1155/2019/2851380 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A WFS1 variant disrupting acceptor splice site uncovers the impact of alternative splicing on beta cell apoptosis in a patient with Wolfram syndrome.
Diabetologia
January 2025
Unit of β Cell Biology, Diabetes Research Institute, IRCCS San Raffaele Hospital, Milan, Italy.
Aims/hypothesis: Wolfram syndrome 1 (WS1) is an inherited condition mainly manifesting in childhood-onset diabetes mellitus and progressive optic nerve atrophy. The causative gene, WFS1, encodes wolframin, a master regulator of several cellular responses, and the gene's mutations associate with clinical variability. Indeed, nonsense/frameshift variants correlate with more severe symptoms than missense/in-frame variants.
View Article and Find Full Text PDFMultifocal Retinocytoma Associated With Intronic Acceptor Splice Site Variants in the RB1 Gene.
Cureus
October 2024
Clinical Ophthalmology, Weill Medical College of Cornell University, New York City, USA.
Retinocytomas are benign tumors that arise from mutations in the gene. Previous research describes the appearance of retinocytomas as that of treated retinoblastoma (Rb) lesions, with characteristics such as chorioretinal atrophy, calcification, and a lack of necrosis or mitotic activity on histopathology. We present the unusual case of an asymptomatic seven-year-old girl with two independent translucent masses in the peripheral retina of the right eye (OD) and extensive intraretinal tumor and vitreous seeds.
View Article and Find Full Text PDFGene Editing of the Endogenous Cryptic 3' Splice Site Corrects the RNA Splicing Defect in the β-Thalassemia Mouse Model.
Hum Gene Ther
October 2024
Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Article Synopsis
- - β-thalassemia results from a mutation in the β-globin gene that disrupts RNA splicing, but previous studies showed that correcting this can restore proper mRNA splicing.
- - Researchers used CRISPR-Cas9 to introduce a specific gene edit in a mouse model, successfully leading to correct β-globin mRNA splicing and improving health outcomes.
- - The study found that a gene-editing frequency over 20% significantly enhanced the survival rate of mice with β-thalassemia, highlighting an effective approach for treating this condition.
We report the clinical presentation and genetic screening of a 31-year-old man with dilatation of the aortic root and ascending aorta and a positive family history for aortic dissection and sudden death. A novel heterozygous variant in a splice acceptor site (c.1600-1G>T) of TGFβR2 gene was identified by using a targeted multi-gene panel analysis.
View Article and Find Full Text PDFLoss-of-function variants in UBAP1L cause autosomal recessive retinal degeneration.
Genet Med
June 2024
Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland; Department of Ophthalmology, University Hospital Basel, Basel, Switzerland; Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom. Electronic address:
Purpose: Inherited retinal diseases (IRDs) are a group of monogenic conditions that can lead to progressive blindness. Their missing heritability is still considerable, due in part to the presence of disease genes that await molecular identification. The purpose of this work was to identify novel genetic associations with IRDs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!