Copyright © 2008 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 82, Issue 5, 1217-1222, 01 May 2008
doi:10.1016/j.ajhg.2008.04.001
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Deleterious Mutations in the Zinc-Finger 469 Gene Cause Brittle Cornea Syndrome
Almogit Abu1, 2, Moshe Frydman1, 4, Dina Marek1, 4, Eran Pras3, 4, Uri Nir2, Haike Reznik-Wolf1 and Elon Pras1, 4, 
, 
1 Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer 52621, Israel
2 Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel
3 Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin 70300, Israel
4 Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel
Corresponding authorAbstract
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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