Autosomal recessive liver phosphorylase kinase deficiency caused by a novel splice-site mutation in the gene encoding the liver gamma subunit (PHKG2).

To facilitate mutation analysis of patients with an autosomal recessive form of liver phosphorylase kinase deficiency, the genomic structure of the gene encoding the testis/liver gamma subunit (PHKG2) was established. The gene consist of 10 exons. The translation start site is located in exon 2. Analysis of DNA from two female siblings, affected with liver phosphorylase kinase deficiency, by exon specific amplification followed by direct sequencing, revealed a single donor splice site mutation in the PHKG2 gene, IVS4 + 1(g --> a). The mutation leads to the skipping of exon 4, which results in a frameshift, starting at nucleotide 272, a premature stop codon after 32 additional amino acids, and subsequent loss of the catalytic site. It is concluded that deficiency of phosphorylase kinase in liver of the patients is caused by the IVS4 + 1(g --> a) mutation. In the patients described here, this genotype is associated with development of liver fibrosis.