Journal of Inherited Metabolic Disease

, Volume 25, Issue 1, pp 35–40 | Cite as

Glu274Lys/Gly309Arg Mutation of the Tissue-Nonspecific Alkaline Phosphatase Gene in Neonatal Hypophosphatasia Associated with Convulsions

  • I. Litmanovitz
  • O. Reish
  • T. Dolfin
  • S. Arnon
  • R. Regev
  • G. Grinshpan
  • M. Yamazaki
  • K. Ozono
Article

Abstract

We describe a patient diagnosed with lethal perinatal hypophosphatasia with a unique clinical presentation of convulsions that responded to vitamin B6. Genomic DNA sequence analysis of the tissue-nonspecific alkaline phosphatase (TNSALP) gene revealed two missense mutations: a G-to-A transition resulting in a Glu to Lys at codon 274 (E274K), and a G-to-C transversion resulting in a Gly to Arg at codon 309 (G309R). The first mutation was maternally transmitted and was previously characterized as a moderate one, whereas the latter was paternally transmitted and has not been previously reported. Phenotype/genotype correlation indicates that G309R is a deleterious mutation that can lead to seizures and a lethal outcome, as was demonstrated in our patient.

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Copyright information

© SSIEM and Kluwer Academic Publishers 2002

Authors and Affiliations

  • I. Litmanovitz
    • 3
  • O. Reish
    • 2
    • 3
  • T. Dolfin
    • 1
    • 3
  • S. Arnon
    • 1
    • 3
  • R. Regev
    • 1
    • 3
  • G. Grinshpan
    • 1
  • M. Yamazaki
    • 4
  • K. Ozono
    • 4
  1. 1.Department of NeonatologyMeir Medical CenterKfar Saba
  2. 2.Genetic Institute, Assaf Harofeh Medical CenterIsrael
  3. 3.Affiliated with the Sackler School of MedicineTel-Aviv UniversityIsrael
  4. 4.Department of Environmental MedicineOsaka Medical Center and Research Institute for Maternal and Child HealthIzumi, OsakaJapan

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