title: A MEN2A family with two asymptomatic carriers affected by unilateral renal agenesis.
abstract: Accumulating evidences suggest RET gene's involvement in development of the kidney in mice and humans. Although it is well known that RET mutation causes multiple endocrine neoplasia type 2A (MEN2A), thus far only 3 individuals have been reported to have MEN2A and renal agenesis/dysgenesis. We report a MEN2A family with RET mutation in which two asymptomatic carriers presented with unilateral renal agenesis. A 48-year-old woman underwent total thyroidectomy with regional lymph node dissection in our department for medullary thyroid carcinoma. She had earlier surgical treatment for a left adrenal pheochromocytoma at the age of 45. In the screening for MEN type 2 for her three sons, a CT scan for adrenal pheochromocytoma incidentally found unilateral renal agenesis in two of the sons, one of whom had suffered from Hirschsprung's disease (HSCR). They had contralateral kidneys exhibiting compensatory hypertrophy and normal renal function. Genetic analysis detected C618R RET mutation in the proband and her 3 sons, and no other mutations were found in RET as well as glial cell line-derived neurotrophic factor (GDNF). Our data lend support to the hypothesis that constitutive active RET mutation in MEN type 2 might partially impair RET function and thereby cause loss of function phenotype such as renal agenesis or HSCR.
authors.affiliation: Department of Endocrine Surgery, Fujita Health University School of Medicine, Toyoake 470-1192, Japan.
authors.forename: Yatsuka
authors.initials: Y
authors.lastname: Hibi
authors.forename: Tamae
authors.initials: T
authors.lastname: Ohye
authors.forename: Kimio
authors.initials: K
authors.lastname: Ogawa
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shibata
authors.forename: Chikara
authors.initials: C
authors.lastname: Kagawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Iwase
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000601:surgery; D018276:Carcinoma, Medullary / Q000151:congenital / Q000235:genetics / Q000601:surgery; D000013:Congenital Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D060005:Genotyping Techniques; D006627:Hirschsprung Disease / Q000235:genetics / Q000601:surgery; D006801:Humans; D007668:Kidney / Q000002:abnormalities*; D007674:Kidney Diseases / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000601:surgery; D009154:Mutation; D010375:Pedigree; D010673:Pheochromocytoma / Q000175:diagnosis / Q000235:genetics / Q000601:surgery; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000601:surgery; D014057:Tomography, X-Ray Computed
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human