title: Investigating ANKH and ENPP1 in Slovakian families with chondrocalcinosis.
abstract: Familial articular chondrocalcinosis (CC) was first reported in 1963. It is characterised by multiple calcifications of hyaline and fibrous cartilage in the joints and intervertebral discs. Mutations in ANKH have been identified in several pedigrees as a monogenic cause for this disorder. ANKH is a key protein in pyrophosphate metabolism and is involved in pyrophosphate transport across the cell membrane. The objective of this work was to screen ANKH and ENPP1, two key genes in pyrophosphate metabolism, in Slovakian kindreds with familial CC. DNA samples from 25 individuals (10 affected, 15 unaffected) from 8 families were obtained. The promoter, coding regions and intron-exon boundaries of ANKH and ENPP1 were sequenced. Twelve DNA sequence variants, six in each gene, were identified. All the variants had been previously identified. None segregated with the disease. Our results suggest that neither ANKH nor ENPP1 mutations are the cause of CC in these families, indicating that possibly other major genes are involved in the aethiopathogenesis of this condition in these families.
authors.affiliation: Serviço Especializado de Epidemiologia e Biologia Molecular, Hospital de Santo Espírito, Angra do Heroísmo, Azores.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Couto
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Andrew
authors.initials: A
authors.lastname: Timms
authors.forename: Jacome
authors.initials: J
authors.lastname: Bruges-Armas
authors.forename: Jorge
authors.initials: J
authors.lastname: Sequeiros
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
mesh_terms: D002805:Chondrocalcinosis / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D011756:Diphosphates / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D007438:Introns; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D028061:Phosphate Transport Proteins / Q000235:genetics*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D011755:Pyrophosphatases / Q000235:genetics*; D018154:Slovakia / Q000453:epidemiology
chemical_list: C498770:ANKH protein, human; D011756:Diphosphates; D028061:Phosphate Transport Proteins; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases