Abstract
We analysed the gene of the human α-subunit of liver phosphorylase kinase (PHKA2) in four Japanese families with X-linked liver phosphorylase kinase deficiency type 1 by RT-PCR followed by PCR–single-strand conformation polymorphism and direct DNA sequencing. In this study, two novel mutations (Y116D and 2675A→G) and one mutation previously reported (P1205L) were identified, revealing molecular heterogeneity in Japanese patients. Considering the dissimilarity in phenotype among our patients even with an identical mutation in the PHKA2 gene, it seems that each genetic deficiency in this gene may not be the only factor to determine the clinical heterogeneity in this disease.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Burwinkel B, Shin YS, Bakker HD (1996) Mutation hotspots in the PHKA2 gene in X-linked liver glycogenosis due to phosphorylase kinase deficiency with atypical activity in blood cells (XLG2). Hum Mol Genet 5: 653-658.
Chen Y-T, Burchell A (1995) Glycogen storage diseases. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease, 7th edn, vol. 1. New York: McGraw-Hill, 935-965.
Hendrickx J, Coucke P, Dams E (1995) Mutations in the phosphorylase kinase gene PHKA2 are responsible for X-linked liver glycogen storage disease. Hum Mol Genet 4: 77-83.
Hirono H, Hayasaka K, Sato W, Takahashi T, Takada G (1995) Isolation of cDNA encoding the human liver phosphorylase kinase alpha subunit (PHKA2) and identification of a missense mutation of the PHKA2 gene in a family with liver phosphorylase kinase deficiency. Biochem Mol Biol Int 36: 505-511.
Orita M, Suzuki Y, Sekiya T, Hayashi K (1989) Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics 5: 874-879.
van den Berg IE, van Beurden EA, Malingre HE (1995) X-linked liver phosphorylase kinase deficiency is associated with mutations in the human liver phosphorylase kinase alpha subunit. Am J Hum Genet 56: 381-387.
Willems PJ, Gerver WJ, Berger R, Fernandes J (1990) The natural history of liver glycogenosis due to phosphorylase kinase deficiency: a longitudinal study of 41 patients. Eur J Pediatr 149: 268-271.
Rights and permissions
About this article
Cite this article
Hirono, H., Shoji, Y., Takahashi, T. et al. Mutational analyses in four Japanese families with X-linked liver phosphorylase kinase deficiency type 1. J Inherit Metab Dis 21, 846–852 (1998). https://doi.org/10.1023/A:1005422819207
Issue Date:
DOI: https://doi.org/10.1023/A:1005422819207