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Glu274Lys/Gly309Arg Mutation of the Tissue‐Nonspecific Alkaline Phosphatase Gene in Neonatal Hypophosphatasia Associated with Convulsions
Author(s) -
Litmanovitz I.,
Reish O.,
Dolfin T.,
Ar S.,
Regev R.,
Grinshpan G.,
Yamazaki M.,
Ozono K.
Publication year - 2002
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1023/a:1015121414782
Subject(s) - hypophosphatasia , transversion , missense mutation , alkaline phosphatase , mutation , genotype , biology , genetics , gene , genotype phenotype distinction , phenotype , microbiology and biotechnology , endocrinology , medicine , enzyme , biochemistry
We describe a patient diagnosed with lethal perinatal hypophosphatasia with a unique clinical presentation of convulsions that responded to vitamin B 6 . 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.