Mutations in the Gene Encoding Capillary Morphogenesis Protein 2 Cause Juvenile Hyaline Fibromatosis and Infantile Systemic Hyalinosis
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- 作者：S ; ra Hanks ; Sarah Adams ; Jenny Douglas ; Laura Arbour ; David J. Atherton ; Sevim Balci ; Harald Bode ; Mary E. Campbell ; Murray Feingold ; Gö ; khan Keser ; Wim Kleijer ; Grazia Mancini ; John A. McGrath ; Francesco Muntoni ; Arti N ; a ; M. Dawn Teare ; Matthew Warman ; F. Michael Pope ; Andrea Superti-Furga ; P.
- 刊名：The American Journal of Human Genetics
- 出版年：2003
- 出版时间：October 2003
- 年：2003
- 卷：73
- 期：4
- 页码：791-800
- 全文大小：1369 K
文摘
Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are autosomal recessive conditions characterized by multiple subcutaneous skin nodules, gingival hypertrophy, joint contractures, and hyaline deposition. We previously mapped the gene for JHF to chromosome 4q21. We now report the identification of 15 different mutations in the gene encoding capillary morphogenesis protein 2 (CMG2) in 17 families with JHF or ISH. CMG2 is a transmembrane protein that is induced during capillary morphogenesis and that binds laminin and collagen IV via a von Willebrand factor type A (vWA) domain. Of interest, CMG2 also functions as a cellular receptor for anthrax toxin. Preliminary genotype-phenotype analyses suggest that abrogation of binding by the vWA domain results in severe disease typical of ISH, whereas in-frame mutations affecting a novel, highly conserved cytoplasmic domain result in a milder phenotype. These data (1) demonstrate that JHF and ISH are allelic conditions and (2) implicate perturbation of basement-membrane matrix assembly as the cause of the characteristic perivascular hyaline deposition seen in these conditions.