Hypophosphatasia: molecular testing of 19 prenatal cases and discussion about genetic counseling

Simon-Bouy, Brigitte, Taillandier, Agnès, Fauvert, Delphine, Brun-Heath, Isabelle and Zankl, Andreas (2008) Hypophosphatasia: molecular testing of 19 prenatal cases and discussion about genetic counseling. Prenatal Diagnosis, 28 11: 993-998. doi:10.1002/pd.2088

Author Simon-Bouy, Brigitte
Taillandier, Agnès
Fauvert, Delphine
Brun-Heath, Isabelle
Zankl, Andreas
Title Hypophosphatasia: molecular testing of 19 prenatal cases and discussion about genetic counseling
Journal name Prenatal Diagnosis   Check publisher's open access policy
ISSN 0197-3851
Publication date 2008-11
Sub-type Article (original research)
DOI 10.1002/pd.2088
Volume 28
Issue 11
Start page 993
End page 998
Total pages 6
Place of publication Bognor Regis, England
Publisher John Wiley and Sons
Language eng
Subject 1103 Clinical Sciences
110311 Medical Genetics (excl. Cancer Genetics)
1114 Paediatrics and Reproductive Medicine
Formatted abstract
We studied hypophosphatasia (HP) mutations in 19 cases prenatally detected by ultrasonography without familial history of HP. We correlated the mutations with the reported ultrasound signs, and discussed genetic counseling with regard to the particular dominantly inherited prenatal benign form of HP.

The coding sequence of the tissue nonspecific alkaline phosphatase (TNSALP) gene was analyzed by DNA sequencing, and 3D modeling was used to locate the mutated amino acids with regard to the functional domains of TNSALP.

Although reported ultrasound signs were heterogeneous, two mutated alleles were found in 18 of the 19 cases studied, indicating recessive transmission of the disease. Functional domains of TNSALP were affected by 74% of missense mutations. In all the cases, including one with only a heterozygous mutation, molecular, biological, and familial data do not corroborate the hypothesis of prenatal benign HP. The mutation c.1133A > T observed in the prenatal benign form of HP and common in USA was not found in this series.

The results point out the prenatally detectable allelic heterogeneity of HP. The nature of the detected mutations and the evidence of recessive inheritance do not support these cases being affected with prenatal benign HP. Copyright © 2008 John Wiley & Sons, Ltd.
Keyword hypophosphatasia
perinatal form
genetic counseling
ALPL mutations
alkaline phosphatase
Q-Index Code C1
Q-Index Status Provisional Code
Additional Notes This work was presented in part at the 5th International Alkaline Phosphatase Symposium, May 16-19, 2007, Huningue, France Conference: 5th International Alkaline Phosphatase Symposium, Huningue, France, 16 May 2007 to 19 May 2007.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
UQ Centre for Clinical Research Publications
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Citation counts: TR Web of Science Citation Count  Cited 7 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 13 Jan 2010, 15:01:21 EST by Maria Campbell on behalf of Faculty Of Health Sciences