Journal Article

Autosomal Glycogenosis of Liver and Muscle Due to Phosphorylase Kinase Deficiency is Caused by Mutations in the Phosphorylase Kinase β Subunit (<i>PHKB</i>)

Barbara Burwinkel, Andrea J. Maichele, Øystein Aagenaes, Henk D. Bakker, Aaron Lerner, Yoon S. Shin, Judith A. Strachan and Manfred W. Kilimann

in Human Molecular Genetics

Volume 6, issue 7, pages 1109-1115
Published in print July 1997 | ISSN: 0964-6906
Published online July 1997 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/6.7.1109
Autosomal Glycogenosis of Liver and Muscle Due to Phosphorylase Kinase Deficiency is Caused by Mutations in the Phosphorylase Kinase β Subunit (PHKB)

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Glycogen storage disease due to phosphorylase kinase deficiency occurs in several variants that differ in mode of inheritance and tissue-specificity. This heterogeneity is suspected to be largely due to mutations affecting different subunits and isoforms of phosphorylase kinase. The gene of the ubiquitously expressed β subunit, PHKB, was a candidate for involvement in autosomally transmitted phosphorylase kinase deficiency of liver and muscle. To identify such mutations, the complete PHKB coding sequence was amplified by RT-PCR of RNA isolated from blood samples of patients and analyzed by direct sequencing of PCR products. The characterization of mutations was complemented by PCR of genomic DNA. In one female and four male patients, we identified five independent nonsense mutations (Y418ter; R428ter; Y974H+E975ter; Q656ter in two cases), one single-base insertion in codon N421, one splice-site mutation affecting exon 31, and a large deletion involving the loss of exon 8. Although these severe translation-disrupting mutations occur in constitutively expressed sequences of the only known β subunit gene of phosphorylase kinase, PHKB, they are associated with a surprisingly mild clinical phenotype, affecting virtually only the liver, and relatively high residual enzyme activity of ∼10%.

Journal Article.  5129 words.  Illustrated.

Subjects: Genetics and Genomics

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