title: Compound heterozygosity in a complete erythrocyte bisphosphoglycerate mutase deficiency.
abstract: Erythrocyte bisphosphoglycerate mutase (BPGM) deficiency is a rare disease associated with a decrease in 2,3-diphosphoglycerate concentration. A complete BPGM deficiency was described in 1978 by Rosa et al (J Clin Invest 62:907, 1978) and was shown to be associated with 30% to 50% of an inactive enzyme detectable by specific antibodies and resulting from an 89 Arg-->Cys substitution. The propositus' three sisters exhibited the same phenotype, while his two children had an intermediate phenotype. Samples from the family were examined using polymerase chain reaction and allele-specific oligonucleotide hybridization and sequencing techniques. Amplification of erythrocyte total RNA from the propositus' sister around the 89 mutation indicated the presence of two forms of messenger RNAs, a major form with the 89 Arg-->Cys mutation and a minor form with a normal sequence. Sequence studies of the propositus' DNA samples indicated heterozygosity at locus 89 and another heterozygosity with the deletion of nucleotide C 205 or C 206. Therefore, the total BPGM deficiency results from a genetic compound with one allele coding for an inactive enzyme (mutation BPGM Créteil I) and the other bearing a frameshift mutation (mutation BPGM Créteil II). Examination of the propositus' two children indicated that they both inherited the BPGM Créteil I mutation.
authors.affiliation: INSERM U.91, Hôpital Henri Mondor, Créteil, France.
authors.forename: V
authors.initials: V
authors.lastname: Lemarchandel
authors.forename: V
authors.initials: V
authors.lastname: Joulin
authors.forename: C
authors.initials: C
authors.lastname: Valentin
authors.forename: R
authors.initials: R
authors.lastname: Rosa
authors.forename: F
authors.initials: F
authors.lastname: Galactéros
authors.forename: J
authors.initials: J
authors.lastname: Rosa
authors.forename: M
authors.initials: M
authors.lastname: Cohen-Solal
mesh_terms: D001120:Arginine; D001483:Base Sequence; D001731:Bisphosphoglycerate Mutase / Q000172:deficiency* / Q000235:genetics*; D015139:Blotting, Southern; D003545:Cysteine; D004912:Erythrocytes / Q000201:enzymology*; D005091:Exons; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics
chemical_list: D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D001120:Arginine; D001731:Bisphosphoglycerate Mutase; D003545:Cysteine