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.
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Authors | C Sergi, E Mornet, J Troeger, T Voigtlaender |
Journal | American journal of medical genetics
(Am J Med Genet)
Vol. 103
Issue 3
Pg. 235-40
(Oct 15 2001)
ISSN: 0148-7299 [Print] United States |
PMID | 11745997
(Publication Type: Case Reports, Journal Article)
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Copyright | Copyright 2001 Wiley-Liss, Inc. |
Chemical References |
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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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