Language
English
Publication Date
10-20-2025
Journal
Journal of Medical Genetics
DOI
10.1136/jmg-2025-110681
PMID
40744518
PMCID
PMC12358183
PubMedCentral® Posted Date
7-31-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Background: Inherited retinal diseases (IRDs) are a group of disorders often resulting in progressive vision loss, ultimately leading to blindness. A significant portion of their genetic causes remain unresolved, partly due to undiscovered disease-associated genes or variants. This study aimed to identify novel genetic links to IRDs.
Methods: All patients underwent comprehensive ophthalmological evaluation, including retinal imaging (fundus autofluorescence and macular optical coherence tomography) and electroretinogram testing. Whole exome sequencing and whole genome sequencing were performed on patients with clinically unsolved IRD, and data were analysed using an in-house pipeline to identify causal variants. Subsequently, Sanger sequencing was performed to confirm identified variants.
Results: Three unrelated patients from Europe, Middle East and East Asia were identified with unique late-onset retinal degeneration (Stargardt-like phenotype) associated with biallelic loss-of-function (LoF) variants in C19orf44 (HGNC: 26141), a gene of unknown function. The homozygous variant NM_032207.2:c.549_550del;p.Ser185Profs*2 was identified in two unrelated patients (European and Middle Eastern). Moreover, an East Asian patient had likely compound heterozygous LoF variants (NM_032207.2:c.1168C>T;p.Gln390*/c.976_977del;p.Leu326Lysfs*15).
Conclusions: Our findings establish C19orf44 as a novel disease-causing gene for IRD with Stargardt-like phenotype, expanding the genetic landscape of retinal degeneration.
Keywords
Humans, Retinal Degeneration, Male, Female, Loss of Function Mutation, Middle Aged, Exome Sequencing, Pedigree, Adult, Alleles, Genetic Predisposition to Disease, Tomography, Optical Coherence, Electroretinography, Phenotype, Whole Genome Sequencing, Genetics; Genetics, Medical; Genotype; Ophthalmology
Published Open-Access
yes
Recommended Citation
Hussain, Hafiz Muhammad Jafar; Meng, Wang; Li, Yumei; et al., "Biallelic Loss-of-Function Variants in C19orf44 Lead to Retinal Degeneration" (2025). Faculty and Staff Publications. 4344.
https://digitalcommons.library.tmc.edu/baylor_docs/4344
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Endocrinology, Diabetes, and Metabolism Commons, Medical Sciences Commons, Ophthalmology Commons, Optometry Commons