title: Pyruvate kinase deficiency in France: a 3-year study reveals 27 new mutations.
abstract: Pyruvate kinase (PK) deficiency is the most common enzyme defect affecting the glycolytic pathway of the erythrocyte. Usually, it is clinically silent in heterozygotes but serious disorders are described at birth in homozygotes or compound heterozygotes. Including the mutants herein reported, more than 180 mutations of the PK-LR gene have now been identified. This 3-year study was carried out to detect mutations associated with disease-affecting families. Haematological indices, erythrocyte PK and glucose-6-phosphate dehydrogenase activities were measured. Molecular characterisation of the PK gene mutations included restriction enzyme analysis, mutation scanning and gene sequencing. Among the 56 families studied, nine homozygous cases and 41 different mutations were found. Eight mutations involved a splice site, 31 missense mutations were located in crucial domains of the molecule (catalytic site, cleft between the A and C domains, A/A' interface) and two cases of insertion-deletion were found. In total, 20 new mutations modifying the structure of the enzyme and seven affecting a splice site are reported. PK deficiency is an under diagnosed disease. However, deficiency could be life threatening in perinatal period and we report two lethal cases. These results support the characterisation of PK mutations, and show that prenatal diagnosis can identify affected infants and prepare safer conditions for the birth.
authors.affiliation: Laboratoire de Biochimie et de Génétique, AP-HP, Hôpital Henri-Mondor, Creteil, France. serge.pissard@im3.inserm.fr
authors.forename: Serge
authors.initials: S
authors.lastname: Pissard
authors.forename: Isabelle
authors.initials: I
authors.lastname: Max-Audit
authors.forename: Laurent
authors.initials: L
authors.lastname: Skopinski
authors.forename: Aurélie
authors.initials: A
authors.lastname: Vasson
authors.forename: Pascal
authors.initials: P
authors.lastname: Vivien
authors.forename: Catherine
authors.initials: C
authors.lastname: Bimet
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.forename: Frederic
authors.initials: F
authors.lastname: Galacteros
authors.forename: Henri
authors.initials: H
authors.lastname: Wajcman
mesh_terms: D000745:Anemia, Hemolytic, Congenital / Q000201:enzymology / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004912:Erythrocytes / Q000201:enzymology; D005838:Genotype; D005954:Glucosephosphate Dehydrogenase / Q000097:blood; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D010641:Phenotype; D011770:Pyruvate Kinase / Q000097:blood / Q000172:deficiency* / Q000235:genetics*
chemical_list: D005954:Glucosephosphate Dehydrogenase; D011770:Pyruvate Kinase