Deleterious Mutations in the Zinc-Finger 469 Gene Cause Brittle Cornea Syndrome

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2008 May 3

PMID 18452888

Citations 54

Authors

Almogit Abu

Moshe Frydman

Dina Marek

Eran Pras

Uri Nir

Haike Reznik-Wolf

Elon Pras

Affiliations

Soon will be listed here.

Abstract

Brittle cornea syndrome (BCS) is an autosomal-recessive disorder characterized by a thin cornea that tends to perforate, causing progressive visual loss and blindness. Additional systemic symptoms such as joint hypermotility, hyperlaxity of the skin, and kyphoscoliosis place BCS among the connective-tissue disorders. Previously, we assigned the disease gene to a 4.7 Mb interval on chromosome 16q24. In order to clone the BCS gene, we first narrowed the disease locus to a 2.8 Mb interval and systematically sequenced genes expressed in connective tissue in this chromosomal segment. We have identified two frameshift mutations in the Zinc-Finger 469 gene (ZNF469). In five unrelated patients of Tunisian Jewish ancestry, we found a 1 bp deletion at position 5943 (5943 delA), and in an inbred Palestinian family we detected a single-nucleotide deletion at position 9527 (9527 delG). The function of ZNF469 is unknown. However, a 30% homology to a number of collagens suggests that it could act as a transcription factor involved in the synthesis and/or organization of collagen fibers.

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