A Novel Germ-Line Point Mutation in RET Exon 8 (Gly533Cys) in a Large Kindred with Familial Medullary Thyroid Carcinoma

Familial medullary thyroid carcinoma is related to germ-line mutations in the RET oncogene, mainly in cysteine codon 10 or 11, whereas noncysteine mutations in codons 13–15 are rare. We now report a new missense point mutation in exon 8 of the RET gene (1597G→T) corresponding to a Gly533Cys substitu...

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Published inThe journal of clinical endocrinology and metabolism Vol. 88; no. 11; pp. 5438 - 5443
Main Authors Álvares Da Silva, Adriana M., Maciel, Rui M. B., Dias Da Silva, Magnus R., Toledo, Silvia R. C., De Carvalho, Marcos B., Cerutti, Janete M.
Format Journal Article
LanguageEnglish
Published Bethesda, MD Oxford University Press 01.11.2003
Copyright by The Endocrine Society
Endocrine Society
Subjects
Age
Biological and medical sciences
Codons
Endocrinopathies
Hyperplasia
Malignant tumors
Medical sciences
Mutation
Patients
Point mutation
Ret protein
Thyroid cancer
Thyroid carcinoma
Thyroid. Thyroid axis (diseases)
Thyroidectomy
Tropical medicine
South America
Brazil
America
Endocrinopathy
Human
Family study
Germ line
Point mutation
Thyroid diseases
Medullary carcinoma
Candidate gene
Malignant tumor
Genetic determinism
Genetic disease
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Summary:Familial medullary thyroid carcinoma is related to germ-line mutations in the RET oncogene, mainly in cysteine codon 10 or 11, whereas noncysteine mutations in codons 13–15 are rare. We now report a new missense point mutation in exon 8 of the RET gene (1597G→T) corresponding to a Gly533Cys substitution in the cystein-rich domain of RET protein in 76 patients from a 6-generation Brazilian family with 229 subjects, with ascendants from Spain. It is likely that the mutation causes familial medullary thyroid carcinoma (FMTC), because no other mutation was found in RET, the mutation cosegregates with medullary thyroid carcinoma (MTC) or C cell hyperplasia (CCH) in patients subjected to surgery, and family members without the mutation are clinically unaffected. The histological analysis of 35 cases submitted to thyroidectomy revealed that 21 patients had MTC after the age of 40 yr and 8 before the age of 40 yr, 4 presented MTC or CCH before the age of 18 yr, 2 died due to MTC at the age of 53 and 60 yr, and CCH was found in a 5-yr-old child, suggesting a clinical heterogeneity. To improve the diagnosis of FMTC, analysis of exon 8 of RET should be considered in families with no identified classical RET mutations.
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ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2003-030997