Your browser doesn't support javascript.
loading
RET 634 germline/gonadal mosaicism generating a second pathogenic amino acid change in multiple endocrine neoplasia type 2A.
Valente, Flávia O F; Camacho, Cléber P; Lindsey, Susan C; Yang, Ji H; Kunii, Ilda S; Santos, Roberto B; Kizys, Marina M L; Cerutti, Janete M; Dias-da-Silva, Magnus R; Maciel, Rui M B.
Afiliación
  • Valente FOF; Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
  • Camacho CP; Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
  • Lindsey SC; Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
  • Yang JH; Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
  • Kunii IS; Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
  • Santos RB; Division of Endocrinology, Pontifícia Universidade Católica de Campinas, Campinas, São Paulo, Brazil.
  • Kizys MML; Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
  • Cerutti JM; Genetic Basis of Thyroid Tumor Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
  • Dias-da-Silva MR; Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
  • Maciel RMB; Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
Am J Med Genet A ; 194(7): e63576, 2024 07.
Article en En | MEDLINE | ID: mdl-38407483
ABSTRACT
Genetic testing for germline RET pathogenic variants, which cause the Multiple Endocrine Neoplasia Type 2 (MEN2) syndrome, has become crucial in managing patients with medullary thyroid carcinoma (MTC). Classically, RET heterozygous missense pathogenic variants are transmitted in a Mendelian autosomal dominant pattern, of which germline/gonadal mosaicism has never been reported. We report the novel occurrence of a MEN2A patient's family in which the siblings inherited three different RET 634 genotypes wild type (p.Cys634), p.Cys634Gly or p.Cys634Arg heterozygous pathogenic variants. We hypothesized that germline/gonadal mosaicism, derived from an inherited + early somatic mutation in the mother or a double de novo mutation during maternal embryogenesis, led to this rare event in the RET gene. Exome analysis of the proband's deceased mother's paraffin-embedded thyroid tissue confirmed the three nucleotides in the same 634 codon position. For the first time, we describe germline/gonadal mosaicism in RET, generating a second pathogenic amino acid change in the same codon causing MEN2A. Our finding shows that RET parental mosaicism, confirmed by somatic exome sequencing, might explain discrepant genotype cases in siblings with inherited cancers.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linaje / Mutación de Línea Germinal / Neoplasia Endocrina Múltiple Tipo 2a / Proteínas Proto-Oncogénicas c-ret / Mosaicismo Límite: Adult / Female / Humans / Male Idioma: En Revista: Am J Med Genet A Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linaje / Mutación de Línea Germinal / Neoplasia Endocrina Múltiple Tipo 2a / Proteínas Proto-Oncogénicas c-ret / Mosaicismo Límite: Adult / Female / Humans / Male Idioma: En Revista: Am J Med Genet A Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos