Mutations in FYCO1 identified in families with congenital cataracts

Hira Iqbal, Shahid Y. Khan, Lin Zhou, Bushra Irum, Muhammad Ali, Mariya R. Ahmed, Mohsin Shahzad, Muhammad Hassaan Ali, Muhammad Asif Naeem, Sheikh Riazuddin, J. Fielding Hejtmancik, S. Amer Riazuddin

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: This study was designed to identify the pathogenic variants in three consanguineous families with congenital cataracts segregating as a recessive trait. Methods: Consanguineous families with multiple individuals manifesting congenital cataracts were ascertained. All participating members underwent an ophthalmic examination. A small aliquot of the blood sample was collected from all participating individuals, and genomic DNAs were extracted. Homozygosity-based linkage analysis was performed using short tandem repeat (STR) markers. The haplotypes were constructed with alleles of the STR markers, and the two-point logarithm of odds (LOD) scores were calculated. The candidate gene was sequenced bidirectionally to identify the disease-causing mutations. Results: Linkage analysis localized the disease interval to chromosome 3p in three families. Subsequently, bidirectional Sanger sequencing identified two novel mutations—a single base deletion resulting in a frameshift (c.3196delC; p.His1066IlefsTer10) mutation and a single base substitution resulting in a nonsense (c.4270C>T; p.Arg1424Ter) mutation—and a known missense (c.4127T>C, p.Leu1376Pro) mutation in FYCO1. All three mutations showed complete segregation with the disease phenotype and were absent in 96 ethnically matched control individuals. Conclusions: We report two novel mutations and a previously reported mutation in FYCO1 in three large consanguineous families. Taken together, mutations in FYCO1 contribute nearly 15% to the total genetic load of autosomal recessive congenital cataracts in this cohort.

Original languageEnglish (US)
Pages (from-to)334-344
Number of pages11
JournalMolecular vision
Volume26
StatePublished - 2020

ASJC Scopus subject areas

  • Ophthalmology

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