Tohoku J. Exp. Med., 2003, 200 (1)

Detection of PHKA2 Gene Mutation in Four Japanese
Patients with Hepatic Phosphorylase
Kinase Deficiency

KYOKO BAN, KOHACHIRO SUGIYAMA, KENJI GOTO,
FUMIHIKO MIZUTANI and HAJIME TOGARI

Department of Pediatrics, Neonatology and Congenital Disorders, Nagoya City University, Graduate School of Medical Sciences, Nagoya 467-8601

We analyzed the PHKA2 gene in four Japanese families with hepatic phosphorylase kinase (PhK) deficiency. Mutational analysis of PHKA2 cDNA was performed by reverse-transcribed polymerase chain reaction (RT-PCR) and direct sequencing, and each mutation was confirmed on the genomic DNA. In boys with low erythrocyte PhK activity (i.e., X-linked liver glycogenosis [XLG] type I), deletion of exon 2 (splice site mutation of 79-1 G>T) or nonsense mutation of Q1169X or R497X was identified. However, missense mutation of R295C was identified in one boy with normal erythrocyte PhK activity (i.e., XLG type II). This mutation was not found in 100 control alleles, and was considered responsible for presentation of the XLG type II phenotype. Excluding Q1169X, all mutations detected in this study represented novel mutations. All mothers were found to be heterozygous carriers of the mutations. Gene analysis was confirmed to represent a useful procedure for diagnosing XLG type II, for which liver biopsy had previously been required to detect hepatic PhK deficiency.

keywords —— liver glycogenosis; phosphorylase kinase deficiency; PHKA2; mutation

© 2003 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2003, 200, 47-53

Address for reprints: Kyoko Ban, Department of Pediatrics, Neonatology and Congenital Disorders, Nagoya City University, Graduate School of Medical Sciences, Nagoya 467-8601, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.

e-mail: kban@med.nagoya-cu.ac.jp