Brachydactyly type C caused by a homozygous missense mutation in the prodomain of CDMP1

Schwabe G., Turkmen S., Leschik G., Palanduz S., Stover B., Goecke T., ...Daha Fazla

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, sa.4, ss.356-363, 2004 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: Sayı: 4
  • Basım Tarihi: 2004
  • Doi Numarası: 10.1002/ajmg.a.20349
  • Dergi Adı: AMERICAN JOURNAL OF MEDICAL GENETICS PART A
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.356-363
  • Anahtar Kelimeler: brachydactyly, CDMP1, Gdf5, TGF-beta, prodomain, MCPP, CAMURATI-ENGELMANN-DISEASE, RECEPTOR TYROSINE KINASE, TGF-BETA-SUPERFAMILY, LOCUS HETEROGENEITY, GENE, CHONDRODYSPLASIA, IDENTIFICATION, MORPHOGENESIS, MECHANISMS, HYPOPLASIA
  • İstanbul Üniversitesi Adresli: Hayır

Özet

Brachydactyly type C (BDC) is characterized by shortening of the middle phalanges of the index, middle, and little finger with hyperphalangy, usually of the index and middle finger. Heterozygous mutations. of the cartilage derived morphogenetic protein-1 (CDMP1) resulting in a loss of function have been reported in BDC. We here describe a large kindred with a semi-dominant form of BDC and pronounced ulnar deviation of the second and third digits. In this family a novel homozygous missense mutation was identified (517A > G) changing methionine to valine at amino acid position 173. The mutation is located within a highly conserved seven amino acid region of the prodomain of CDMP1. Hand radiographs of heterozygous mutation carriers showed mild shortening of the metacarpals IV and V; a finding confirmed by the analysis of their metacarpophalangeal profiles (MCPPs). The mutation described here points toward an important function of the prodomain for the folding, secretion, and availability of biologically active CDMP1. (C) 2003 Wiley-Liss, Inc.