Autosomal Recessive Phosphorylase Kinase Deficeincy in Liver, Caused by Mutations in the Gene Encoding the ß subunit (PHKB)

Inge E.T. van den Berg, Ellen A.C.M. van Beurden, Johannis B.D. de Klerk, Otto P. van Diggelen, Helga E.M. Malingré, Marijke M. Boer, Ruud Berger

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17 Citations (Scopus)

Abstract

The association of autosomal recessive phosphorylase kinase deficiency in liver of a 3½-year-old female child with mutations in the gene encoding the common part of the p subunit of phosphorylase kinase is reported. The proband had a severe deficiency of phosphorylase kinase in liver, while the phosphorylase kinase activity in erythrocytes was only slightly diminished. She had no symptoms of muscle involvement. The complete coding sequences of the liver γ subunit and of the β subunit of phosphorylase kinase of the proband were analyzed for the presence of mutations, by either reverse-transcribed PCR or SSCP analysis. Three deviations from the normal sequence were found in the region encoding the common part of the β subunit of phosphorylase kinase—namely, a 1827G→A (W609X) transition, a 2309A→G (Y770C) transition, and a deletion of nucleotides 2896–2911—whereas no mutations were detected in the sequence encoding the liver β subunit of phosphorylase kinase. The 1827G→A mutation and the deletion both result in the formation of early stop codons. Investigation of DNA showed that the deletion is caused by a splice-acceptor site mutation (IVS30−1, g→t). Family analysis revealed that the 1827G→A and IVS30−1, g→t substitutions are located on different parental chromosomes and that compound heterozygosity for these mutations segregates with the disease. The 2309A→G mutation was detected in 2%–3% of the normal population. Thus, it is concluded that the deficiency of phosphorylase kinase in this proband is caused by compound heterozygosity for the 1827G→A and the IVS30−1, g→t mutations and that the 2309A→G mutation is a polymorphism. This implies that a defect in the sequence encoding the common part of the β subunit of phosphorylase kinase may present as liver phosphorylase kinase deficiency.
Original languageEnglish
Pages (from-to)539-546
Number of pages8
JournalAmerican Journal of Human Genetics
Volume61
Issue number3
DOIs
Publication statusPublished - Sept 1997

Research programs

  • EMC MGC-02-96-01
  • EMC MM-01-54-01

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