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

Objective 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...

Full description

Saved in:

Bibliographic Details
Published in:	Prenatal diagnosis Vol. 28; no. 11; pp. 993 - 998
Main Authors:	Simon-Bouy, Brigitte, Taillandier, Agnès, Fauvert, Delphine, Brun-Heath, Isabelle, Serre, Jean-Louis, Armengod, Carmen G., Bialer, Martin G., Mathieu, Michèle, Cousin, Jacques, Chitayat, David, Liebelt, Jan, Feldman, Barbara, Gérard-Blanluet, Marion, Körtge-Jung, Stefani, King, Cath, Laivuori, Hannele, Le Merrer, Martine, Mehta, Sarju, Jern, Christina, Sharif, Saba, Prieur, Fabienne, Gillessen-Kaesbach, Gabriele, Zankl, Andreas, Mornet, Etienne
Format:	Journal Article
Language:	English
Published:	Chichester, UK John Wiley & Sons, Ltd 01-11-2008 Wiley
Subjects:	Alkaline Phosphatase Alkaline Phosphatase - genetics ALPL mutations Biological and medical sciences Bone and Bones Bone and Bones - embryology Bone and Bones - pathology Delivery. Postpartum. Lactation embryology Female Fundamental and applied biological sciences. Psychology Genes Genes, Recessive Genetic Counseling Genetic Counseling - methods genetics Genetics of eukaryotes. Biological and molecular evolution Gynecology. Andrology. Obstetrics Humans Hypophosphatasia Hypophosphatasia - diagnostic imaging Hypophosphatasia - embryology Hypophosphatasia - genetics MEDICAL AND HEALTH SCIENCES Medical sciences MEDICIN OCH HÄLSOVETENSKAP methods Molecular and cellular biology Mutation pathology perinatal form Pregnancy Prenatal Recessive ultrasonography Ultrasonography, Prenatal ultrasounds Sonography Alkaline phosphatase Enzyme Gynecology ultrasounds Phosphoric monoester hydrolases Neonatology Perinatal Metabolic diseases Esterases Enzymopathy Hypophosphatasia Genetic disease Prenatal Genetic counseling Echography ALPL mutations Hydrolases Genetics Mutation Molecular biology Ultrasound perinatal form: genetic counseling
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Objective 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. Method 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. Results 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. Conclusion 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.
Bibliography:	ArticleID:PD2088 This work was presented in part at the 5th International Alkaline Phosphatase Symposium, May 16-19, 2007, Huningue, France Agence de la Biomédecine and from the supportive group Hypophosphatasie Europe istex:FB22439F680AAB29B5F26FB4160004F6182A373A ark:/67375/WNG-963NZ05H-D This work was presented in part at the 5th International Alkaline Phosphatase Symposium, May 16–19, 2007, Huningue, France ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0197-3851 1097-0223
DOI:	10.1002/pd.2088