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Molekularbiologie, Grundlagenforschung und Diagnose des Morbus Hirschsprung

Molecular biology, basic research and diagnosis of Hirschsprung’s disease

  • Schwerpunkt: Gastrointestinale Motilitätsstörungen
  • Published:
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Zusammenfassung

Das RET-Proto-Onkogen ist das zentrale für die Entstehung eines M. Hirschsprung verantwortliche Gen, wobei RET-Mutationen auch bei anderen pathologischen Läsionen vorkommen. Bei Hirschsprung-Patienten konnten eine Reihe verschiedener RET-Mutationen festgestellt werden. Besondere Aufmerksamkeit sollte denjenigen Patienten gewidmet werden, die Mutationen der Exone für die entscheidenden Zysteinreste aufweisen, welche für MEN2A prädisponieren. Bei diesen Patienten kann der M. Hirschsprung selten mit der Entwicklung neuroendokriner Tumoren, wie mit einem medullären Schilddrüsenkarzinom oder einer MEN2A assoziiert sein. Daher ist eine prophylaktische Thyreoidektomie dann ratsam, wenn eine tumorassoziierte RET-Mutation gefunden wurde. In MEN2A/Hirschsprung-Familien können die RET-Mutationsanalyse, Tumor-Screening und ggf. eine prohylaktische Thyreoidektomie wie bei MEN2A empfohlen werden. Der multigenetische Ursprung des M. Hirschsprung in Abwesenheit einer spezifischen „Standard-Hirschsprung-Mutation“ macht eine genetische Routinediagnostik unmöglich.

Abstract

The proto-oncogene RET is the major gene responsible for Hirschsprung’s disease (HSCR), with RET mutations also implied in different pathologies. A variety of mutations of the RET proto-oncogene have been detected in HSCR patients. Special attention should be paid to rare patients who carry mutations of one of the critical cysteine residues of these exons, known to predispose to MEN2A. In these cases, HSCR can be associated with the development of neuroendocrine tumors such as medullary thyroid carcinoma (MTC) or MEN2A, for which a prophylactic thyroidectomy is advisable in the presence of a tumor causing RET mutation. In combined MEN2A/HSCR families, RET gene testing, tumor screening and prophylactic thyroidectomy are indicated as in MEN2A. The multigenic origin of HSCR and the absence of a “standard” RET mutation associated with HSCR currently make a routine molecular diagnosis impossible.

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Martucciello, G., Luinetti, O., Romano, P. et al. Molekularbiologie, Grundlagenforschung und Diagnose des Morbus Hirschsprung. Pathologe 28, 119–124 (2007). https://doi.org/10.1007/s00292-007-0897-7

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