Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10.
Hum Mutat
; 32(1): 51-8, 2011 Jan.
Article
de En
| MEDLINE
| ID: mdl-20979234
Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for clinical-risk profiles. Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were studied. A total of 340 subjects from 103 families, age 4-86, were registered. There were 21 distinct single nucleotide germline mutations located in codons 609 (45 subjects), 611 (50), 618 (94), and 620 (151). MTC was present in 263 registrants, pheochromocytoma in 54, and hyperparathyroidism in 8 subjects. Of the patients with MTC, 53% were detected when asymptomatic, and among those with pheochromocytoma, 54%. Penetrance for MTC was 4% by age 10, 25% by 25, and 80% by 50. Codon-associated penetrance by age 50 ranged from 60% (codon 611) to 86% (620). More advanced stage and increasing risk of metastases correlated with mutation in codon position (609â620) near the juxtamembrane domain. Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Exons
/
Mutation germinale
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Néoplasie endocrinienne multiple de type 2a
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Pénétrance
/
Protéines proto-oncogènes c-ret
Type d'étude:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Child
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Child, preschool
/
Female
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Humans
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Male
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Middle aged
Langue:
En
Journal:
Hum Mutat
Sujet du journal:
GENETICA MEDICA
Année:
2011
Type de document:
Article
Pays d'affiliation:
Allemagne
Pays de publication:
États-Unis d'Amérique