Journal Article

Mutation Hotspots in the <i>PHKA2 G</i> Gene in X-Linked Liver Glycogenosis Due to Phosphorylase Kinase Deficienc with Atypical Activity in Blood Cells (XLG2)

Barbara Burwinkel, Yoon S. Shin, Henk D. Bakker, Johann Deutsch, María José Lozano, Irène Maire and Manfred W. Kilimann

in Human Molecular Genetics

Volume 5, issue 5, pages 653-658
Published in print May 1996 | ISSN: 0964-6906
Published online May 1996 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/5.5.653
Mutation Hotspots in the PHKA2 G Gene in X-Linked Liver Glycogenosis Due to Phosphorylase Kinase Deficienc with Atypical Activity in Blood Cells (XLG2)

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In five cases of X-linked liver glycogenosis subtype 2 (XLG2), we have identified mutations in the gene encoding the liver isoform of the phosphorylase kinase α subunit (PHKA2). XLG2 is a rare variant of X-linked phosphorylase kinase (Phk) deficiency of the liver. Whereas in the more common form of X-linked hepatic Phk deficiency, XLG1, the enzyme's activity is decreased both in liver and in blood cells, Phk activity in XLG2 is low in liver but normal or even enhanced in blood cells. Although missense, nonsense and splicesite mutations in the PHKA2gene were recently identified in several cases of XLG1, no mutations have yet been described for XLG2 and a molecular explanation for the peculiar biochemical phenotype of XLG2 has been lacking. All mutations found in the present study result in non-conservative amino acid replacements of residues that are absolutely conserved between the αL, αM and β subunits of Phk [H132P, H132Y, R186H (twice) and D299G]. Strikingly, in two pairs of cases the mutations affect the same codon. These results demonstrate that: (i) XLG2 is caused by mutations in PHKA2 and is therefore allelic with XLG1; and (ii) XLG2 mutations appear to cluster in limited sequence regions or even individual codons.

Journal Article.  3993 words.  Illustrated.

Subjects: Genetics and Genomics

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