ePrints

A Homozygous CPSF1 Variant Causes Congenital Cataract, Intellectual Disability and Hyperphagia

Lookup NU author(s): Dr Ana TopfORCiD

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

Abstract

© 2026 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.The cleavage and polyadenylation specific factor 1 (CPSF1) gene encodes a subunit of the cleavage and polyadenylation specificity factor (CPSF), a multi-protein complex essential for mRNA 3′ end processing. The role of CPSF1 in retinal function and eye development has been demonstrated using zebrafish models and heterozygous variants in CPSF1 have been reported in early-onset high myopia (MIM: 618827). Here, we present a patient with bilateral congenital cataracts and intellectual disability with a novel homozygous missense variant (c.3817G>C; p.Asp1273His) in CPSF1. This amino acid change is predicted to change the protein structure with likely damaging effect. Proteomic results in white blood cells revealed increased CPSF1 protein abundance and dysregulated proteins in pathways linked to cellular signalling processes, protein degradation, and exosome biology. To our knowledge, this is the first report of recessive CPSF1-related disease in humans presenting as a case with congenital cataracts, intellectual disability, and hyperphagia.

Publication metadata

Author(s): Kilicarslan OA, Gangfuss A, Hentschel A, Kolbel H, Muhmann D, Topf A, Stohr M, Chen L, Horvath R, Thompson R, Schara-Schmidt U, Kurth I, Lochmuller H, Kraft F, Polavarapu K, Roos A

Publication type: Article

Publication status: Published

Journal: Clinical Genetics

Year: 2026

Pages: epub ahead of print

Online publication date: 07/01/2026

Acceptance date: 19/12/2025

ISSN (print): 0009-9163

ISSN (electronic): 1399-0004

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1111/cge.70130

DOI: 10.1111/cge.70130

PubMed id: 41498167

Altmetrics

Share