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Perinatal hypophosphatasia: radiology, pathology and molecular biology studies in a family harboring a splicing mutation (648+1A) and a novel missense mutation (N400S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene.

Abstract
We report on a postmortem diagnosis of perinatal lethal hypophosphatasia, an inborn error of metabolism characterized by a liver/bone/kidney alkaline phosphatase (ALP)-related defective bone mineralization due to mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. Radiological and pathological studies identified a perinatal lethal hypophosphatasia showing a generalized bone mineralization defect including asymmetry of the cervical vertebral arches in a 22 +4 weeks' gestation fetus. Both parents revealed low serum ALP activities supporting the diagnosis. Sequencing analysis of the TNSALP gene showed two heterozygous mutations, 648+1A, a mutation affecting the donor splice site in exon 6, and N400S, a novel missense mutation in exon 11, located near the active site and very close to histidins 364 and 437, two crucial residues of the active site. Sequencing of exons 6 and 11 in the parents showed that 648+1A was from maternal origin and N400S from paternal origin. DNA-based prenatal testing in the subsequent pregnancy following a chorionic villous sampling performed at 10 weeks of gestation showed no mutation and a healthy infant was born at term.
AuthorsC Sergi, E Mornet, J Troeger, T Voigtlaender
JournalAmerican journal of medical genetics (Am J Med Genet) Vol. 103 Issue 3 Pg. 235-40 (Oct 15 2001) ISSN: 0148-7299 [Print] United States
PMID11745997 (Publication Type: Case Reports, Journal Article)
CopyrightCopyright 2001 Wiley-Liss, Inc.
Chemical References
  • Alkaline Phosphatase
Topics
  • Alkaline Phosphatase (analysis, genetics)
  • Base Sequence
  • Calcification, Physiologic
  • Female
  • Femur (pathology)
  • Fetus (abnormalities)
  • Humans
  • Hypophosphatasia (diagnostic imaging, genetics, pathology)
  • Infant Mortality
  • Infant, Newborn
  • Male
  • Mutation
  • Pedigree
  • Pregnancy
  • Radiography
  • Tissue Distribution

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