Bleeding and non-bleeding phenotypes in patients with GGCX gene mutations

Watzka M., Geisen C., Scheer M., Wieland R., Wiegering V., Doerner T., ...Daha Fazla

THROMBOSIS RESEARCH, cilt.134, sa.4, ss.856-865, 2014 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 134 Sayı: 4
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1016/j.thromres.2014.07.004
  • Dergi Adı: THROMBOSIS RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.856-865
  • Anahtar Kelimeler: GGCX, Mutation, Osteocalcin, MGP, Bone, GLUTAMYL-CARBOXYLASE GENE, CONGENITAL COMBINED DEFICIENCY, PROPEPTIDE BINDING-SITE, VITAMIN-K DEFICIENCY, MATRIX GLA PROTEIN, PSEUDOXANTHOMA ELASTICUM, COMPOUND HETEROZYGOSITY, WARFARIN EMBRYOPATHY, VKORC1 HAPLOTYPES, IX PROPEPTIDE
  • Ondokuz Mayıs Üniversitesi Adresli: Evet

Özet

Functional limitations for the vitamin K cycle, caused either by mutations in gamma-glutamyl carboxylase or vitamin K epoxide reductase genes, result in hereditary deficiency of vitamin K-dependent coagulation factors (VKCFD1 and VKCFD2, respectively). Patients suffering from VKCFD often share several other anatomical irregularities which are not related to haemostasis. Here we report on nine patients, eight of them previously unreported, who presented with VKCFD1. All were examined with special attention to vitamin K-dependent coagulation factors as well as to bone and heart development and to other anatomical signs of embryonal vitamin K deficiency. In total, we detected ten mutations in the gamma-glutamyl carboxylase gene of which seven have not been previously reported. Most interestingly, additional non-bleeding phenotypes were observed in all patients including midfacial hypoplasia, premature osteoporosis, cochlear hearing loss, heart valve defects, pulmonary stenosis, or pseudoxanthoma elasticum-like phenotype. Undercarboxylated matrix Gla protein, osteocalcin, and periostin appear to be responsible for these defects which are also observed in cases of fetal warfarin syndrome. (C) 2014 Elsevier Ltd. All rights reserved.