Identification of novel missense mutations (Phe310Leu and Gly439Arg) in a neonatal case of hypophosphatasia

The Journal of Clinical Endocrinology and Metabolism
Keiichi OzonoM Nakayama

Abstract

Hypophosphatasia is associated with a defect of the tissue-non-specific alkaline phosphatase gene. We performed a mutational analysis in a surviving patient diagnosed at birth as having hypophosphatasia, on the basis of a low level of serum alkaline phosphatase (ALP) activity and characteristic radiographical findings. She had two sisters, one of whom died of respiratory failure complicated by perinatal hypophosphatasia; the other seemed healthy, with a relatively low activity level of ALP. The patient's parents also had low ALP activity. Sequence analysis of the tissue-nonspecific alkaline phosphatase gene was performed, using genomic DNA and total RNA from the skin fibroblasts of the patient and the peripheral mononuclear cells of her parents. The conversion of Phe to Leu at codon 310 (F310L) and Gly to Arg at 439 (G439R) were identified in the patient. Interestingly, the reconstructive experiments demonstrated that the F310L mutant exhibited an ALP activity level 65% of the normal level, whereas the mutant G439R had no activity. Moreover, the digestion by StuI, after a PCR using complementary DNA extracted from fibroblasts of the patient and lymphocytes of her father, revealed a relatively low messenger RNA level of F310L. T...Continue Reading

Citations

Jun 19, 2008·The Journal of Clinical Endocrinology and Metabolism·David A StevensonMichael P Whyte
Nov 5, 2002·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Hisashi WatanabeIsao Ishikawa
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Aug 7, 2002·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Sonia Di MauroJose Luis Millán
Dec 15, 2011·Journal of Bone and Mineral Metabolism·Kei-Ichiro IidaYukihide Iwamoto
Jan 20, 2016·European Journal of Internal Medicine·Leyre Riancho-ZarrabeitiaJosé A Riancho
Oct 16, 2015·European Journal of Pediatrics·Yoko OkazakiKeiichi Ozono
Jan 1, 2010·Clinical Pediatric Endocrinology : Case Reports and Clinical Investigations : Official Journal of the Japanese Society for Pediatric Endocrinology·Akari Nakamura-UtsunomiyaMasao Kobayashi
May 6, 2008·Molecular Genetics and Metabolism·Hideo OrimoTakashi Shimada
Oct 1, 2008·The Journal of Pediatrics·Juhi KumarRobert P Woroniecki
Feb 28, 2017·Bone·Michael P Whyte
Jan 28, 2017·American Journal of Medical Genetics. Part a·Jair TenorioPablo Lapunzina
Nov 11, 2019·Calcified Tissue International·Toshimi MichigamiKeiichi Ozono

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