A Homozygous CPSF1 Variant Causes Congenital Cataract, Intellectual Disability and Hyperphagia
Ozge Aksel Kilicarslan1,2, Andrea Gangfuß3, Andreas Hentschel4
1Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Clinical Genetics
|January 7, 2026
Summary
A novel homozygous variant in the cleavage and polyadenylation specific factor 1 (CPSF1) gene caused a rare recessive disease. This condition presented with congenital cataracts, intellectual disability, and hyperphagia in a patient.
Area of Science:
- Genetics
- Molecular Biology
- Ophthalmology
Background:
- The cleavage and polyadenylation specific factor 1 (CPSF1) gene is crucial for mRNA 3' end processing.
- CPSF1's role in retinal function and eye development is established; heterozygous variants are linked to high myopia.
Purpose of the Study:
- To report a novel homozygous missense variant in CPSF1.
- To characterize a new human genetic disorder associated with CPSF1 deficiency.
Main Methods:
- Genetic sequencing to identify the CPSF1 variant.
- Proteomic analysis of patient's white blood cells.
- Bioinformatic prediction of variant's functional impact.
Main Results:
- Identified a novel homozygous missense variant (c.3817G>C; p.Asp1273His) in CPSF1.
- The variant is predicted to damage protein structure and function.
- Proteomics revealed increased CPSF1 abundance and dysregulated cellular pathways.
Conclusions:
- This is the first report of a recessive CPSF1-related disorder in humans.
- The findings expand the phenotypic spectrum of CPSF1-associated diseases to include congenital cataracts, intellectual disability, and hyperphagia.
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