Hypophosphatasia is a rare inherited disorder characterized by defective bone and teeth mineralization and deficiency of serum and bone alkaline phosphatase activity. The frequency of the disease has been estimated to 1/100,000 for severe forms. The symptoms are highly variable in their clinical expression, which ranges from stillbirth without mineralized bone to early loss of tooth without bone symptoms (Whyte 1994). The transmission of severe forms is autosomal recessive while milder forms may be transmitted as dominant or recessive autosomal traits. The disease is due to mutations in the alkaline phosphatase liver-type (ALPL) gene, also named the TNSALP gene. See more informations in Orphanet. The ALPL gene, localized on chromosome 1p36-34 (Greenberg et al. 1990), consists of 12 exons distributed over 50 kb (Weiss et al. 1988) and is subject to very strong allelic heterogeneity. To date, at least 216 distinct mutations and 12 polymorphisms are known, (see the list of mutations and the list of polymorphisms). The patients examined mostly consisted of European, North-American, Australian and Japanese individuals.
Exon 1 | Exon 2 | Exon 3 | Exon 4 | Exon 5 | Exon 6 | Exon 7 | Exon 8 | Exon 9 | Exon 10 | Exon 11 | Exon 12 | Large deletions
A97G+c.348_349insACCGTC /G309R
Utsch et al., 2009
Nomenclature : see the nomenclature section below. Reference : reference of the publication describing the mutation. Clinical form in patient : clinical form of the patient in whom the mutation was detected for the first time. Genotype of patient : genotype of the patient in whom the mutation was detected for the first time (non-standardized nomenclature) ? uncharacterized mutation (undetected mutation without molecular or pedigree evidence of dominant transmission). N normal allele (dominant mutation on the other chromosome, evidenced by molecular or pedigree data. %WT : alkaline phosphatase activity of cells transfected with mutated cDNAs, expressed in percentage of the activity found in cells transfected with wild type (WT) cDNA. ref : reference reporting transfections experiments. unp. : unpublished. E.coli : conservation in E.coli of residues affected by mutations. na, not applicable ; +, conserved residue ; -, residue not conserved.
Non-standardized nomenclature: according to Weiss et al. 1988; The nomenclature takes into account of a 17-residues signal peptide, i.e. the ATG initiation codon is numbered as residue minus (-)17. Standardized nomenclature: according to the recommandations of the Human Genome Variation Society (HGVS): the first codon is the ATG initiation codon. p: protein numbering; c: nucleotide numbering of the coding sequence.
