-Case Reports-

Prenatal Genetic Diagnosis of Severe Perinatal (Lethal) Hypophosphatasia

Atsushi Watanabe^1,2, Seiichi Yamamasu³, Toshiya Shinagawa⁴, Yumi Suzuki¹, Hidehiko Miyake^1,4, Toshiyuki Takeshita⁴, Hideo Orimo² and Takashi Shimada^1,2

¹Division of Clinical Genetics, Nippon Medical School Hospital
²Department of Biochemistry and Molecular Biology, Nippon Medical School
³Department of Obstetrics and Gynecology, Osaka City University
⁴Department of Obstetrics and Gynecology, Nippon Medical School

Hypophosphatasia is an inherited disorder characterized by defective bone mineralization and a deciency in tissue-nonspecic alkaline phosphatase (TNSALP) activity. This disorder is caused by various mutations of the TNSALP gene. We report here the prenatal diagnosis of the perinatal (lethal) type of hypophosphatasia in a sibling of an affected infant. The infant had been found to have hypophosphatasia on the basis of both clinical and radiologic manifestations and the nding of a homozygous single T nucleotide deletion at 1559 (1559delT) of the TNSALP gene on molecular analysis. Both parents were carriers with a heterozygous mutation in the same position, although they were not consanguineous. After their next child had been conceived, fetal genomic DNA was extracted from cultured cells of amniotic fluid at 15 weeks' gestation. The fetus had a homozygous 1559delT mutation. An ultrasonography examination at 19 weeks' gestation showed marked hypomineralization of all bony structures. A prenatal genetic diagnosis for hypophosphatasia in combination with ultrasonography is thus considered to be useful for confirming the diagnosis of hypophosphatasia, which presents with a wide variety of phenotypes. As a result, prenatal genetic counseling for hypophosphatasia with collaboration between obstetricians and clinical genetics teams.

J Nippon Med Sch 2007; 74: 65-69

Keywords
Prenatal diagnosis, hypophosphatasia, genetic diagnosis, ultrasonography, genetic counseling

Correspondence to
Atsushi Watanabe, MD, Division of Clinical Genetics, Nippon Medical School Hospital, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
aw3703@nms.ac.jp

Received, November 29, 2006
Accepted, December 20, 2006