Genetic heterogeneity in 30 German patients with oculopharyngeal muscular dystrophy |
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Authors: | T Müller M Deschauer F Kolbe-Fehr St Zierz |
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Institution: | 1. Klinik und Poliklinik für Neurologie, Martin-Luther-Universit?t,
Halle-Wittenberg, Ernst-Grube-Str. 40, 06097, Halle (Saale), Germany
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Abstract: | Oculopharyngeal muscular dystrophy (OPMD) is due to short elongations of a polyalanine tract in the poly(A) binding protein
nuclear 1 (PABPN1) gene. Originally GCG expansions in which (GCG)6 is extended to (GCG)7–13 were found. Subsequently five further genotypes with additional GCA– and GCG–trinucleotides were identified in single OPMD
patients. This indicated larger genetic heterogeneity and showed that unequal crossing–over and not replication slippage must
be the underlying mechanism of elongation.We performed sequencing of the PABPN1 gene in 30 German OPDM index patients to determine the exact genotype. The original GCG expansion ranging from (GCG)8 to (GCG)11 was found in 22 patients. In 8 patients, however, three different elongated alleles other than classical (GCG)7–13 were observed. Two of these genotypes had already been identified in Japanese patients. One genotype was recently identified
showing (GCG)6 followed by inserted (GCA)3GCG in four unrelated patients. This study further supports the theory of unequal crossing over as the molecular mechanism
leading to elongation. It shows that other genotypes than classical (GCG)7–13 are rather common in German OPMD patients. The data imply that there is no single founder effect in German OPMD patients.
Drs. Müller and Deschauer contributed equally to this work. |
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Keywords: | oculopharyngeal muscular dystrophy OPMD polyalanine disease unequal crossing– over PABPN1 |
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