caa a22 4500 397575297 CHVBK 20180308164854.0 cr unu---uuuuu 161202e199605 xx s 000 0 eng 10.1093/hmg/5.5.653 doi (NATIONALLICENCE)oxford-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) [Elektronische Daten] [Barbara Burwinkel, Yoon S. Shin, Henk D. Bakker, Johann Deutsch, María José Lozano, Irène Maire, Manfred W. Kilimann] 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. © 1996 Oxford University Press Burwinkel Barbara Institut für Physiologische Chemie, Medizinische Fakultät, Ruhr-Universität Bochum, D-44780 Bochum, Germany aut Shin Yoon S. Stoffwechselzentrum, Dr. v. Haunersches Kinderspital der LMU München, D-80337 München, Germany aut Bakker Henk D. Emma Kinderziekenhuis, Universiteit van Amsterdam, NL-1105 AZ Amsterdam, The Netherlands aut Deutsch Johann Universitätsklinik für Kinder- und Jugendheilkunde, A-8036 Graz, Austria aut José Lozano María Dpto. de Pediatría, Hospital Universitario M. de Valdecilla, Universidad de Cantabria, E-39011 Santander, Spain aut Maire Irène Centre d'Étude des Maladies Métaboliques, Hôpital Debrousse, F-69322 Lyon Cedex 5, France aut Kilimann Manfred W. Institut für Physiologische Chemie, Medizinische Fakultät, Ruhr-Universität Bochum, D-44780 Bochum, Germany aut Human Molecular Genetics Oxford University Press 5/5(1996-05), 653-658 0964-6906 5:5<653 1996 5 hmg https://doi.org/10.1093/hmg/5.5.653 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.5.653 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Burwinkel Barbara Institut für Physiologische Chemie, Medizinische Fakultät, Ruhr-Universität Bochum, D-44780 Bochum, Germany aut NATIONALLICENCE 700 1- Shin Yoon S. Stoffwechselzentrum, Dr. v. Haunersches Kinderspital der LMU München, D-80337 München, Germany aut NATIONALLICENCE 700 1- Bakker Henk D. Emma Kinderziekenhuis, Universiteit van Amsterdam, NL-1105 AZ Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Deutsch Johann Universitätsklinik für Kinder- und Jugendheilkunde, A-8036 Graz, Austria aut NATIONALLICENCE 700 1- José Lozano María Dpto. de Pediatría, Hospital Universitario M. de Valdecilla, Universidad de Cantabria, E-39011 Santander, Spain aut NATIONALLICENCE 700 1- Maire Irène Centre d'Étude des Maladies Métaboliques, Hôpital Debrousse, F-69322 Lyon Cedex 5, France aut NATIONALLICENCE 700 1- Kilimann Manfred W. Institut für Physiologische Chemie, Medizinische Fakultät, Ruhr-Universität Bochum, D-44780 Bochum, Germany aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/5(1996-05), 653-658 0964-6906 5:5<653 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford