RESUMO
BACKGROUND: We previously identified a four-generation family with medullary thyroid cancer (MTC) and a germline p.Y791F RET mutation whose cancer lacked a strong genotype-phenotype correlation. The entire gene coding region of the RET gene should be sequenced when genotype-phenotype discrepancies are observed in patients with multiple endocrine neoplasia type 2 (MEN 2), even if a RET hotspot mutation has been identified. METHODS: A new genetic test was performed in the index case of this family with the p.Y791F RET germline mutation. The entire coding region of the RET gene was investigated by direct sequencing of PCR products. Once a mutation was identified, the target exon was sequenced in all at-risk relatives. RESULTS: An additional p.C634Y germline mutation in the RET gene was identified in the reported family. The double mutation occurred in cis and segregated with the phenotype. Through the Brazilian Genetic Screening Program developed at our institution, we additionally report the combination of these two mutations (p.C634Y/p.Y791F) in the RET gene in four other unrelated families. The overall penetrance of MTC and pheochromocytoma in patients with the p.C634Y/p.Y791F mutations was 79% and 13%, respectively. CONCLUSION: Our data emphasises that a comprehensive analysis of the RET gene may reveal multiple germline mutations in MEN 2 patients who exhibit an atypical clinical course of the disease.
Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Carcinoma Medular/genética , Neoplasia Endócrina Múltipla Tipo 2a/genética , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Brasil , Calcitonina/sangue , Carcinoma Neuroendócrino , Feminino , Estudos de Associação Genética , Genótipo , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Feocromocitoma/genéticaRESUMO
Con el objeto de evaluar el procedimiento de biopsia-succión de la mucosa del intestino delgado dirigida bajo control endoscópico, fueron estudiados 47 pacientes. Sobre un total de 121 muestras obtenidos resultaron adecuadas para diagnóstico 114 muestras (94,2%). Este procedimiento resultó ser efectivo, rápido y seguro para el estudio de la patología de la mucosa yeyunal (AU)
Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Intestino Delgado/patologia , Biópsia por Agulha/instrumentação , Intubação/métodos , EndoscopiaRESUMO
Con el objeto de evaluar el procedimiento de biopsia-succión de la mucosa del intestino delgado dirigida bajo control endoscópico, fueron estudiados 47 pacientes. Sobre un total de 121 muestras obtenidos resultaron adecuadas para diagnóstico 114 muestras (94,2%). Este procedimiento resultó ser efectivo, rápido y seguro para el estudio de la patología de la mucosa yeyunal
Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Biópsia por Agulha/instrumentação , Endoscopia , Intestino Delgado/patologia , IntubaçãoRESUMO
The technical difficulties of the procedures for jejunal biopsy are a waste of time. In the present paper we consider the suction biopsy of small bowel with the Olympus equipment, under endoscopic control. We studied 47 patients, mean age 46 years old (range 22-70) with clinical suggestion of malabsorption. In all patients, we tried to obtain 3 samples, in 31 (66%) we obtained the 3, in 8 (17%) we obtained 2 and in 2 (4.2%) no samples. With this procedure we had 121 samples; from these 114 (94.2%) were useful for diagnosis. We had no complications. The small bowel biopsy with Olympus system was fast, sure and effective.
Assuntos
Biópsia por Agulha/métodos , Endoscopia , Jejuno/patologia , Adulto , Idoso , Biópsia por Agulha/instrumentação , Humanos , Síndromes de Malabsorção/patologia , Pessoa de Meia-IdadeRESUMO
The technical difficulties of the procedures for jejunal biopsy are a waste of time. In the present paper we consider the suction biopsy of small bowel with the Olympus equipment, under endoscopic control. We studied 47 patients, mean age 46 years old (range 22-70) with clinical suggestion of malabsorption. In all patients, we tried to obtain 3 samples, in 31 (66
) we obtained the 3, in 8 (17
) we obtained 2 and in 2 (4.2
) no samples. With this procedure we had 121 samples; from these 114 (94.2
) were useful for diagnosis. We had no complications. The small bowel biopsy with Olympus system was fast, sure and effective.
