title: Homozygosity for R87H missense mutation and for a rare intron 7 DNA variant (7054G --> A) in the PROC genes of three siblings initially classified as heterozygotes for protein C deficiency.
abstract: We report the results of protein C gene (PROC) analysis in a Spanish family with hereditary PC deficiency characterized by the presence of three siblings with PC anticoagulant activity levels clearly below 50% of normal and PC antigen and amidolytic activities between 50 and 75% of normal. Their parents are first cousins and have PC levels between 50 and 80% of normal. Sequence analysis of the whole coding sequence of the PROC gene revealed that the three siblings are double homozygotes for a G to A transition at nucleotide 3203 that replaces arginine 87 by histidine (R87H) and for another G to A transition at nucleotide 7054, in intron 7 (7054G --> A). Both parents and one sister were found to be double heterozygotes for these two mutations. Screening for the intronic mutation in a control group and RT-PCR cDNA studies from ectopically transcribed mRNA indicated that 7054G --> A is most likely a rare but neutral DNA variant. These results and the fact that heterozygosity for the missense R87H mutation has also been found associated with a slightly decreased PC anticoagulant activity in another Spanish family, lead us to conclude that homozygosity for R87H is responsible for the PC deficient phenotype in these three siblings.
authors.affiliation: Molecular Genetics Department, Cancer Research Institute (IRO), Hospital Durani Reynals, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Soria
authors.forename: M
authors.initials: M
authors.lastname: Morell
authors.forename: I
authors.initials: I
authors.lastname: Nicolau
authors.forename: X
authors.initials: X
authors.lastname: Estivill
authors.forename: N
authors.initials: N
authors.lastname: Sala
mesh_terms: D000225:Adenine / Q000737:chemistry; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000235:genetics*; D005091:Exons; D014644:Genetic Variation; D006147:Guanine / Q000737:chemistry; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011486:Protein C / Q000235:genetics*; D020151:Protein C Deficiency
chemical_list: D011486:Protein C; D006147:Guanine; D004247:DNA; D000225:Adenine