Peutz-Jeghers syndrome: 78-year follow-up of the original family

Anne Marie Westerman, Mark M. Entius, Ellen De Baar, Patrick P C Boor, Rita Koole, M. Loes F Van Velthuysen, G. Johan A Offerhaus, Dick Lindhout, Felix W M De Rooij, J. H Paul Wilson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1211-1215
Number of pages5
JournalThe Lancet
Volume353
Issue number9160
DOIs
StatePublished - Apr 10 1999
Externally publishedYes

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Peutz-Jeghers Syndrome
Germ-Line Mutation
Pigmentation
Genes
Exons
Phenotype
Mutation
Heredity
Terminator Codon
Intestinal Obstruction
Polyps
Nose
Codon
Physical Examination
Alleles
Interviews
Morbidity

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Westerman, A. M., Entius, M. M., De Baar, E., Boor, P. P. C., Koole, R., Van Velthuysen, M. L. F., ... Wilson, J. H. P. (1999). Peutz-Jeghers syndrome: 78-year follow-up of the original family. The Lancet, 353(9160), 1211-1215. https://doi.org/10.1016/S0140-6736(98)08018-0

Peutz-Jeghers syndrome : 78-year follow-up of the original family. / Westerman, Anne Marie; Entius, Mark M.; De Baar, Ellen; Boor, Patrick P C; Koole, Rita; Van Velthuysen, M. Loes F; Offerhaus, G. Johan A; Lindhout, Dick; De Rooij, Felix W M; Wilson, J. H Paul.

In: The Lancet, Vol. 353, No. 9160, 10.04.1999, p. 1211-1215.

Research output: Contribution to journalArticle

Westerman, AM, Entius, MM, De Baar, E, Boor, PPC, Koole, R, Van Velthuysen, MLF, Offerhaus, GJA, Lindhout, D, De Rooij, FWM & Wilson, JHP 1999, 'Peutz-Jeghers syndrome: 78-year follow-up of the original family', The Lancet, vol. 353, no. 9160, pp. 1211-1215. https://doi.org/10.1016/S0140-6736(98)08018-0
Westerman AM, Entius MM, De Baar E, Boor PPC, Koole R, Van Velthuysen MLF et al. Peutz-Jeghers syndrome: 78-year follow-up of the original family. The Lancet. 1999 Apr 10;353(9160):1211-1215. https://doi.org/10.1016/S0140-6736(98)08018-0
Westerman, Anne Marie ; Entius, Mark M. ; De Baar, Ellen ; Boor, Patrick P C ; Koole, Rita ; Van Velthuysen, M. Loes F ; Offerhaus, G. Johan A ; Lindhout, Dick ; De Rooij, Felix W M ; Wilson, J. H Paul. / Peutz-Jeghers syndrome : 78-year follow-up of the original family. In: The Lancet. 1999 ; Vol. 353, No. 9160. pp. 1211-1215.
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