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

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• 作者：Almogit Abu ; Moshe Frydman ; Dina Marek ; Eran Pras ; Uri Nir ; Haike Reznik-Wolf ; Elon Pras
• 刊名：The American Journal of Human Genetics
• 出版年：2008
• 出版时间：9 May 2008
• 年：2008
• 卷：82
• 期：5
• 页码：1217-1222
• 全文大小：700 K

文摘

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.