Progressive juvenile-onset punctate cataracts caused by mutation of the γD-crystallin gene

Dietrich A. Stephan, Elizabeth Gillanders, Deborah Vanderveen, Diana Freas-Lutz, Graeme Wistow, Andreas D. Baxevanis, Christiane M. Robbins, Ann Vanauken, Matthew I. Quesenberry, Joan Bailey-Wilson, Suh Hang Hank Juo, Jeffrey M. Trent, Lois Smith, Michael J. Brownstein

Research output: Contribution to journalArticlepeer-review

Abstract

Cataracts are a significant public health problem. Here, we describe the genetic alteration responsible for a progressive form of cataract, segregating as an autosomal dominant trait in a three-generation pedigree. Unlike most autosomal dominant cataracts, these are not clinically apparent at birth but are initially observed in the first year or two of life. The opacification evolves relatively slowly, generally necessitating removal of the lens in childhood or early adolescence. A genome-wide search in our kindred revealed linkage at 2q33-35 where the γ-crystallin gene cluster resides. A single base alteration resulting in an Arg- 14 → Cys (R14C) substitution in γD-crystallin was subsequently identified. Protein modeling suggests that the effect of this mutation is a subtle one, affecting the surface properties of the crystallin molecule rather than its tertiary structure, consistent with the fact that the patients' lenses are normal at birth. This is the first gene defect shown to be responsible for a noncongenital progressive cataract, and studying the defective protein should teach us more about the mechanisms underlying cataract formation.

Original languageEnglish (US)
Pages (from-to)1008-1012
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number3
DOIs
StatePublished - Feb 2 1999

ASJC Scopus subject areas

  • General

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