Deleterious mutations in the Zinc-Finger 469 gene cause brittle cornea syndrome.
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.
Abu
Almogit
A
Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer 52621, Israel.
Frydman
Moshe
M
Marek
Dina
D
Pras
Eran
E
Nir
Uri
U
Reznik-Wolf
Haike
H
Pras
Elon
E
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*
D024022:Fibrillar Collagens; D014157:Transcription Factors; C530065:ZNF469 protein, human