title: Prenatal diagnosis of familial lethal hypophosphatasia using imaging, blood enzyme levels, chorionic villus sampling and archived fetal tissue.
abstract: Hypophosphatasia is an inheritable disorder characterized by defective bone mineralization and a deficiency of tissue-nonspecific alkaline phosphatase (TNSALP) activity. Screening for mutations in the TNSALP gene allows genetic counseling and prenatal diagnosis of the disease in families with severe forms of hypophosphatasia. A 33-year-old, gravida 4, para 3 Japanese woman was referred to Nagoya City University Hospital for prenatal genetic counseling because of two previous occurrences of fetal bone anomalies. The molecular examination showed that the fetus was homozygous for the TNSALP gene mutation c.1559delT, each parent being heterozygous. Genetic counseling was offered and at the next pregnancy, chorionic villus sampling was performed, whereupon genetic analysis confirmed that the fetus did not carry the familial mutation c.1559delT. Postnatal molecular genetic analysis using the cord tissue can provide a diagnosis of lethal hypophosphatasia and prenatal genetic diagnosis of the TNSALP gene allows time for parental counseling and delivery planning.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. og.n.suz@med.nagoya-cu.ac.jp
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Suzumori
authors.forename: Etienne
authors.initials: E
authors.lastname: Mornet
authors.forename: Eita
authors.initials: E
authors.lastname: Mizutani
authors.forename: Shintaro
authors.initials: S
authors.lastname: Obayashi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ozaki
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sugiura-Ogasawara
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood / Q000235:genetics*; D002113:Calcification, Physiologic / Q000235:genetics; D015193:Chorionic Villi Sampling; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: C548267:ALPL protein, human; D000469:Alkaline Phosphatase