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Familial associations in medullary thyroid carcinoma with Hirschsprung disease: the role of the RET-C620 "Janus" genetic variation.
J Pediatr Surg. 2010 Feb; 45(2):393-6.JP

Abstract

INTRODUCTION

Hirschsprung disease (HSCR) is associated with the later development of multiple endocrine neoplasia (MEN2), because RET gene variations are associated with both conditions. Specifically, HSCR-MEN2 cosegregation mostly relates to the cysteine-rich area at the RET-620 (the "Janus gene").

AIM

The aim of this study was to explore the clinical and genetic associations of HSCR-MEN2 in a cohort of HSCR patients.

METHODS

RET gene variation was evaluated by heteroduplex single-strand conformational polymorphism analysis and validated with automated sequencing techniques in HSCR patients (including 18 kindreds). Those with RET C620 variations were subjected to familial evaluation for coexisting HSCR-MEN2.

RESULTS

A cohort of 118 patients with HSCR (n = 89) or medullary thyroid carcinoma (n = 29) were studied, including 3 families where a RET-620 point mutation was identified. No C618, C609, or C611 variations were detected. In 1 remarkable 6-generational family (family 3), HSCR in early generations seemed to be later replaced by MEN2A. In the other 2 families with total colonic aganglionosis, a relative with a medullary thyroid carcinoma was identified.

CONCLUSION

Gene mutation in the RET-620 position carries significant risk and may be part of a targeted investigation of high-risk areas in HSCR. We propose an alternative hypothesis of endoplasmic reticulum control to explain the changing phenotypic expression.

Authors+Show Affiliations

Division of Paediatric Surgery, Faculty of Health Sciences, University of Stellenbosch, PO Box 19063, Tygerberg 7505, South Africa. swm@sun.ac.zaNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

20152359

Citation

Moore, Sam W., and Monique Zaahl. "Familial Associations in Medullary Thyroid Carcinoma With Hirschsprung Disease: the Role of the RET-C620 "Janus" Genetic Variation." Journal of Pediatric Surgery, vol. 45, no. 2, 2010, pp. 393-6.
Moore SW, Zaahl M. Familial associations in medullary thyroid carcinoma with Hirschsprung disease: the role of the RET-C620 "Janus" genetic variation. J Pediatr Surg. 2010;45(2):393-6.
Moore, S. W., & Zaahl, M. (2010). Familial associations in medullary thyroid carcinoma with Hirschsprung disease: the role of the RET-C620 "Janus" genetic variation. Journal of Pediatric Surgery, 45(2), 393-6. https://doi.org/10.1016/j.jpedsurg.2009.10.080
Moore SW, Zaahl M. Familial Associations in Medullary Thyroid Carcinoma With Hirschsprung Disease: the Role of the RET-C620 "Janus" Genetic Variation. J Pediatr Surg. 2010;45(2):393-6. PubMed PMID: 20152359.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Familial associations in medullary thyroid carcinoma with Hirschsprung disease: the role of the RET-C620 "Janus" genetic variation. AU - Moore,Sam W, AU - Zaahl,Monique, PY - 2009/10/23/received PY - 2009/10/27/accepted PY - 2010/2/16/entrez PY - 2010/2/16/pubmed PY - 2010/4/23/medline SP - 393 EP - 6 JF - Journal of pediatric surgery JO - J Pediatr Surg VL - 45 IS - 2 N2 - INTRODUCTION: Hirschsprung disease (HSCR) is associated with the later development of multiple endocrine neoplasia (MEN2), because RET gene variations are associated with both conditions. Specifically, HSCR-MEN2 cosegregation mostly relates to the cysteine-rich area at the RET-620 (the "Janus gene"). AIM: The aim of this study was to explore the clinical and genetic associations of HSCR-MEN2 in a cohort of HSCR patients. METHODS: RET gene variation was evaluated by heteroduplex single-strand conformational polymorphism analysis and validated with automated sequencing techniques in HSCR patients (including 18 kindreds). Those with RET C620 variations were subjected to familial evaluation for coexisting HSCR-MEN2. RESULTS: A cohort of 118 patients with HSCR (n = 89) or medullary thyroid carcinoma (n = 29) were studied, including 3 families where a RET-620 point mutation was identified. No C618, C609, or C611 variations were detected. In 1 remarkable 6-generational family (family 3), HSCR in early generations seemed to be later replaced by MEN2A. In the other 2 families with total colonic aganglionosis, a relative with a medullary thyroid carcinoma was identified. CONCLUSION: Gene mutation in the RET-620 position carries significant risk and may be part of a targeted investigation of high-risk areas in HSCR. We propose an alternative hypothesis of endoplasmic reticulum control to explain the changing phenotypic expression. SN - 1531-5037 UR - https://www.unboundmedicine.com/medline/citation/20152359/Familial_associations_in_medullary_thyroid_carcinoma_with_Hirschsprung_disease:_the_role_of_the_RET_C620_"Janus"_genetic_variation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3468(09)00879-3 DB - PRIME DP - Unbound Medicine ER -