title: Founder mutation Arg485Pro led to recurrent compound heterozygous GGCX genotypes in two German patients with VKCFD type 1.
abstract: Congenital combined deficiency of the vitamin-K-dependent coagulation factors (VKCFD) represents a rare autosomal recessive inherited bleeding disorder caused by mutations in either the gamma-glutamyl carboxylase gene (VKCFD type 1) or the vitamin K epoxide reductase gene (VKCFD type 2). Four different mutations of the gamma-glutamyl carboxylase gene (GGCX) have so far been reported in three unrelated patients with VKCFD type 1. Here we report on a fourth patient who presented with two compound heterozygous missense mutations of the GGCX gene, His404Pro and Arg485Pro. The His404Pro mutation has not been described previously, while the Arg485Pro mutation has been reported in another compound heterozygous VKCFD type 1 patient from Germany. Most interestingly, haplotype analysis revealed that Arg485Pro is due to a founder mutation, suggesting that this mutation is present in the German population at some low frequency. The founder mutation explains that the only two compound heterozygous VKCFD type 1 patients known today originated from Germany.
authors.affiliation: Institute of Human Genetics, Biocenter, Am Hubland, University Würzburg, Würzburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Rost
authors.forename: Christof
authors.initials: C
authors.lastname: Geisen
authors.forename: Andreas
authors.initials: A
authors.lastname: Fregin
authors.forename: Erhard
authors.initials: E
authors.lastname: Seifried
authors.forename: Clemens R
authors.initials: CR
authors.lastname: Müller
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
mesh_terms: D000328:Adult; D019735:Carbon-Carbon Ligases / Q000235:genetics* / Q000502:physiology; D017124:Conserved Sequence / Q000235:genetics; D005260:Female; D018703:Founder Effect; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D006899:Mixed Function Oxygenases / Q000172:deficiency / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014812:Vitamin K / Q000008:administration & dosage*; D064417:Vitamin K Epoxide Reductases
chemical_list: D014812:Vitamin K; D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase