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.
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 -
