Zurzeit sind zwei Kernhüllenproteine bekannt, das Lamin A/C und Emerin, bei denen Mutationen zu phänotypisch definierbaren Erkrankungen führen. Mutationen des auf dem Chromosom 1q21.2 - 1q21.3 kartierten LMNA-Gens bewirken Veränderungen der Proteine Lamin A und C. Die klinischen Manifestationsformen einer Mutation auf dem LMNA-Gen umfassen die Hauptmann-Thannhauser-Muskeldystrophie, die Gliedergürtelmuskeldystrophie 1B, die dilatative Kardiomyopathie 1A und die familiäre partielle Lipodystrophie Typ Dunnigan mit autosomal-dominantem Erbgang sowie die autosomal-rezessiv vererbte hereditäre sensomotorische Neuropathie Typ 2B (HSMN 2B). Die Erkrankungen mit autosomal-dominantem Erbgang zeigen nicht selten Phänotypen, deren Symptome sich überlappen können. Die Emery-Dreifuss-Muskeldystrophie mit X-chromosomalem Erbgang ist klinisch kaum von der Hauptmann-Thannhauser-Muskeldystrophie unterscheidbar. Molekulargenetisch liegt dieser Erkrankung jedoch eine Mutation des STA-Gens auf Chromosom Xq28 zugrunde, welches für Emerin, ein anderes Kernhüllenprotein, kodiert. Hinsichtlich der verschiedenen Mutationen im LMNA-Gen ist es bislang noch ungeklärt, wie Art und Lokalisation und eventuell modifizierende Faktoren den Phänotyp beeinflussen.
Abstract
There are two proteins of the nuclear envelope, lamin A/C and emerin, in which mutations are known to cause phenotypic distinguishable disorders. Mutations in the LMNA gene, mapped to chromosome 1q21.2 - 21.3, encoding nuclear proteins lamin A and C cause various disorders with autosomal-dominant inheritance. Some of these disorders show a phenotypical expression with overlapping symptoms as in Hauptmann-Thannhauser muscular dystrophy, limb girdle muscular dystrophy 1B, dilatative cardiomyopathy 1A, and rarely in the familial partiell lipodystrophy Typ Dunnigan, a metabolic disorder. Furthermore, mutations in the LMNA gene were recently found to cause the autosomal-recessive Charcot-Marie-Tooth disorder Type 2B (HSMN 2B) without muscular or metabolic involvement. The Xq28-linked Emery-Dreifuss muscular dystrophy due to mutations in the STA-gene encoding emerin is clinically not distinguishable from Hauptmann-Thannhauser muscular dystrophy. Concerning the different mutations it is an unsolved question how the kind and location as well as modifying factors are able to influence the phenotype.
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