Germ-Line Mutation Analysis in Patients with Multiple Endocrine Neoplasia Type 1 and Related Disorders
| Autor: | Brigitte Emperauger, Pierre Goudet, Alain Calender, Patrick Gaudray, Patricia Niccoli, Olivier Chabre, Catherine Bauters, Janine Salandre, Patrick Cougard, Sophie Giraud, Jean Louis Peix, Gilbert M. Lenoir, David E. Goldgar, Michel Vallotton, Françoise Duron, Nicole Porchet, Olga Serova-Sinilnikova, Brigitte Delemer, Alain Meyrier, Nathalie Buisson, Michel Rodier, Emile Sarfati, Christine Waterlot, Charles Proye, Yin Y. Shugart, Bernard Conte-Devolx, Philippe Emy, Vincent Rohmer, Guillaume Cadiot, Jean Paul Riou, Sylvie Guichard, Jean-Pierre Aubert, Michel Assayag, Marie-Christine Vantyghem, Frédéric Leprat, Arnaud Murat, Virginie Wautot, Philippe Caron, Philippe Chanson, Chang X. Zhang, Michel Pugeat |
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| Rok vydání: | 1998 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities endocrine system endocrine system diseases Positional cloning Nonsense mutation Mutation Missense Predisposition Biology medicine.disease_cause Germline mutation Proto-Oncogene Proteins Endocrine tumors Multiple Endocrine Neoplasia Type 1 medicine Genetics Humans Point Mutation MEN1 Genetics(clinical) Multiple endocrine neoplasia Germ-Line Mutation Genetics (clinical) Mutation(s) Sequence Deletion Mutation Neoplasia Genetic Carrier Screening Point mutation Multiple Endocrine Neoplasia Menin Exons medicine.disease Penetrance Introns Neoplasm Proteins Pedigree Amino Acid Substitution Female Research Article |
| Zdroj: | The American Journal of Human Genetics. 63(2):455-467 |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/301953 |
| Popis: | Summary Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome predisposing to tumors of the parathyroid, endocrine pancreas, anterior pituitary, adrenal glands, and diffuse neuroendocrine tissues. The MEN1 gene has been assigned, by linkage analysis and loss of heterozygosity, to chromosome 11q13 and recently has been identified by positional cloning. In this study, a total of 84 families and/or isolated patients with either MEN1 or MEN1-related inherited endocrine tumors were screened for MEN1 germ-line mutations, by heteroduplex and sequence analysis of the MEN1 gene–coding region and untranslated exon 1. Germ-line MEN1 alterations were identified in 47/54 (87%) MEN1 families, in 9/11 (82%) isolated MEN1 patients, and in only 6/19 (31.5%) atypical MEN1-related inherited cases. We characterized 52 distinct mutations in a total of 62 MEN1 germ-line alterations. Thirty-five of the 52 mutations were frameshifts and nonsense mutations predicted to encode for a truncated MEN1 protein. We identified eight missense mutations and five in-frame deletions over the entire coding sequence. Six mutations were observed more than once in familial MEN1. Haplotype analysis in families with identical mutations indicate that these occurrences reflected mainly independent mutational events. No MEN1 germ-line mutations were found in 7/54 (13%) MEN1 families, in 2/11 (18%) isolated MEN1 cases, in 13/19 (68.5%) MEN1-related cases, and in a kindred with familial isolated hyperparathyroidism. Two hundred twenty gene carriers (167 affected and 53 unaffected) were identified. No evidence of genotype-phenotype correlation was found. Age-related penetrance was estimated to be >95% at age >30 years. Our results add to the diversity of MEN1 germ-line mutations and provide new tools in genetic screening of MEN1 and clinically related cases. |
| Databáze: | OpenAIRE |
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