title: Deleterious mutations in the Zinc-Finger 469 gene cause brittle cornea syndrome.
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.
authors.affiliation: Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer 52621, Israel.
authors.forename: Almogit
authors.initials: A
authors.lastname: Abu
authors.forename: Moshe
authors.initials: M
authors.lastname: Frydman
authors.forename: Dina
authors.initials: D
authors.lastname: Marek
authors.forename: Eran
authors.initials: E
authors.lastname: Pras
authors.forename: Uri
authors.initials: U
authors.lastname: Nir
authors.forename: Haike
authors.initials: H
authors.lastname: Reznik-Wolf
authors.forename: Elon
authors.initials: E
authors.lastname: Pras
mesh_terms: D003316:Corneal Diseases / Q000235:genetics*; D024022:Fibrillar Collagens / Q000235:genetics; D016368:Frameshift Mutation; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006801:Humans; D010375:Pedigree; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024022:Fibrillar Collagens; D014157:Transcription Factors; C530065:ZNF469 protein, human