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We read with interest the article by Learoyd et al1 concerning genetic testing for multiple endocrine neoplasia, type 2 (MEN 2). We generally agree with the conclusion of this article, but hold a different opinion in regard to the following. The authors state that genetic screening for RET proto-oncogene mutations in MEN 2 is a powerful diagnostic tool and that RET mutation carriers older than 6 years of age should undergo thyroidectomy immediately.
We investigated the spectrum of RET mutations among patients with MEN 2, familial medullary thyroid carcinoma (FMTC), and sporadic medullary thyroid carcinoma (MTC).2 Mutations in nucleotide sequences encoding 1 of 3 specific cysteine residues in the extracellular domain of RET protein were found in 37 of the 38 MEN 2A families and 3 of the 4 FMTC families examined. A mutation at codon 918 was found in the germline DNA of all 5 patients with MEN 2B and in 8 of 22 tumors in patients with sporadic MTC. We detected 4 de novo mutations at codon 634, TGC to TAC or CGC (Cys to Tyr or Arg), and codon 918, ATG to ACG (Met to Thr). We also identified 2 novel somatic mutations in patients with sporadic MTC, 1 at codon 631 (Asp to Gly) and the other at codon 634 (Cys to Arg). Here, I would like to stress that our data show that specific mutations of the RET proto-oncogene are related to the disease phenotype in MEN 2A and FMTC. For example, there is an association between all mutations at codon 634 and pheochromocytoma and parathyroid disease. Mutations at codon 764 and 804 are specific to FMTC. Patients with mutations at codon 634 have a higher recurrence rate than patients with mutations at other codons. The phenotype of the disease and the outcome have been found to vary considerably according to the codon that has mutated. We therefore think that the decision as to the timing of surgery should be based on the site of the mutated codon and estimation of the degree of malignancy of the disease. Because of the possibility of lymph node metastases occurring once MEN 2A patients reach age 6 years, we think that the standard guideline should be to perform thyroidectomy at no later than 5 years of age.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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