AUTOSOMAL RECESSIVE LIVER PHOSPHORYLASE-KINASE DEFICIENCY CAUSED BY ANOVEL SPLICE-SITE MUTATION IN GENE ENCODING THE LIVER GAMMA-SUBUNIT (PHKG2)

To facilitate mutation analysis of patients with an autosomal recessiv e form of liver phosphorylase kinase deficiency, the genomic structure of the gene encoding the testis/liver gamma subunit (PHKG2) was estab lished. The gene consist of 10 exons. The translation start site is lo cated in exon 2. Analysis of DNA from two female siblings, affected wi th liver phosphorylase kinase deficiency, by exon specific amplificati on followed by direct sequencing, revealed a single donor splice site mutation in the PHKG2 gene, IVS4 + 1(g --> a). The mutation leads to h e skipping of exon 4, which results in a frameshift, starting at nucle otide 272, a premature stop codon after 32 additional amino acids, and subsequent loss of the catalytic site. It is concluded that deficienc y of phosphorylase kinase in liver of the patients is caused by the IV S4 + 1(g --> a) mutation. In the patients described here, this genotyp e is associated with development of liver fibrosis. (C) 1997 Academic Press.