Peutz-Jeghers syndrome: 78-year follow-up of the original family
Autor: | Patrick P.C. Boor, Anne Marie Westerman, Mark M. Entius, J. H. Paul Wilson, Felix W. M. de Rooij, Dick Lindhout, G. Johan A. Offerhaus, Ellen de Baar, M. Loes F Van Velthuysen, Rita Koole |
---|---|
Přispěvatelé: | Internal Medicine, Pathology, Clinical Genetics, Other departments |
Jazyk: | angličtina |
Rok vydání: | 1999 |
Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Adolescent DNA Mutational Analysis Mucocutaneous zone Peutz-Jeghers Syndrome Peutz–Jeghers syndrome medicine.disease_cause Frameshift mutation Exon Germline mutation Heredity medicine Humans Allele Child skin and connective tissue diseases Germ-Line Mutation Netherlands Genetics business.industry General Medicine medicine.disease Pedigree Phenotype Child Preschool Female Lentiginosis business Follow-Up Studies |
Zdroj: | Lancet (UK), 353(9160), 1211-1215. Elsevier Ltd. Lancet, 353(9160), 1211-1215. Elsevier Limited |
ISSN: | 0140-6736 |
Popis: | Summary Background The association between heredity, gastrointestinal polyposis, and mucocutaneous pigmentation in Peutz-Jeghers syndrome (PJS) was first recognised in 1921 by Peutz in a Dutch family. This original family has now been followed-up for more than 78 years. We did mutation analysis in this family to test whether the recently identified LKB1 gene is indeed the PJS gene in this family. Methods The original family was retraced and the natural history of PJS was studied in six generations of this kindred by interview, physical examination, chart view, and histological review of tissue specimens. DNA-mutation analysis was done in all available descendants. Findings Clinical features in this family included gastrointestinal polyposis, mucocutaneous pigmentation, nasal polyposis, and rectal extrusion of polyps. Survival of affected family members was reduced by intestinal obstruction and by the development of malignant disease. A novel germline mutation in the LKB1 gene was found to cosegregate with the disease phenotype in the original family. The mutant LKB1 allele carried a T insertion at codon 66 in exon 1 resulting in frameshift and stop at codon 162 in exon 4. Interpretation The morbidity and mortality in this family suggest that PJS is not a benign disease. An inactivating germline mutation in the LKB1 gene is involved in the PJS phenotype in the original and oldest kindred known to be affected by PJS. |
Databáze: | OpenAIRE |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |