Genotype-phenotype correlations in Peutz-Jeghers syndrome

C. I. Amos, M. B. Keitheri-Cheteri, M. Sabripour, C. Wei, Thomas McGarrity, M. F. Seldin, L. Nations, P. M. Lynch, H. H. Fidder, E. Friedman, M. L. Frazier

Research output: Contribution to journalArticle

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Abstract

Background and aims: Peutz-Jeghers syndrome (PJS) is a dominantly inherited disorder often caused by mutations in STK11. Time to onset of symptoms was characterised for a large collection of individuals with PJS who had been tested for STK11 mutations and genotype-phenotype correlations were evaluated. Methods: We characterised mutations in 42 independent probands and also used a historical cohort design to study 51 individuals with Peutz-Jeghers syndrome who had completed self-administered questionnaires. Results: Mutations were detected in 22/32 (69%) probands with PJS and 0/10 probands referred to rule out PJS. Real-time PCR analysis to quantitate DNA failed to detect any large deletions in PJS participants without STK11 mutations. The median time to onset for gastrointestinal symptoms or polypectomy was 13 years of age but showed a wide variability. Gastric polyps were frequent in PJS participants, with a median age at onset of 16 years. Individuals with missense mutations had a significantly later time to onset of first polypectomy (p=0.04) and of other symptoms compared with those participants either with truncating mutations or no detectable mutation. Conclusion: STK11 mutation analysis should be restricted to individuals who meet PJS criteria or their close relatives. Direct sequencing of STK11 yields a high rate of point mutations in individuals who meet phenotypic PJS criteria. Individuals with missense mutations of STK11 typically had a later time to onset for PJS symptoms. The common occurrence of gastric polyps may facilitate chemopreventive studies for this disorder.

Original languageEnglish (US)
Pages (from-to)327-333
Number of pages7
JournalJournal of medical genetics
Volume41
Issue number5
StatePublished - May 1 2004

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Peutz-Jeghers Syndrome
Genetic Association Studies
Mutation
Missense Mutation
Polyps
Stomach
Age of Onset
Point Mutation
Real-Time Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Amos, C. I., Keitheri-Cheteri, M. B., Sabripour, M., Wei, C., McGarrity, T., Seldin, M. F., ... Frazier, M. L. (2004). Genotype-phenotype correlations in Peutz-Jeghers syndrome. Journal of medical genetics, 41(5), 327-333.
Amos, C. I. ; Keitheri-Cheteri, M. B. ; Sabripour, M. ; Wei, C. ; McGarrity, Thomas ; Seldin, M. F. ; Nations, L. ; Lynch, P. M. ; Fidder, H. H. ; Friedman, E. ; Frazier, M. L. / Genotype-phenotype correlations in Peutz-Jeghers syndrome. In: Journal of medical genetics. 2004 ; Vol. 41, No. 5. pp. 327-333.
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Amos, CI, Keitheri-Cheteri, MB, Sabripour, M, Wei, C, McGarrity, T, Seldin, MF, Nations, L, Lynch, PM, Fidder, HH, Friedman, E & Frazier, ML 2004, 'Genotype-phenotype correlations in Peutz-Jeghers syndrome', Journal of medical genetics, vol. 41, no. 5, pp. 327-333.

Genotype-phenotype correlations in Peutz-Jeghers syndrome. / Amos, C. I.; Keitheri-Cheteri, M. B.; Sabripour, M.; Wei, C.; McGarrity, Thomas; Seldin, M. F.; Nations, L.; Lynch, P. M.; Fidder, H. H.; Friedman, E.; Frazier, M. L.

In: Journal of medical genetics, Vol. 41, No. 5, 01.05.2004, p. 327-333.

Research output: Contribution to journalArticle

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AU - Keitheri-Cheteri, M. B.

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AU - Wei, C.

AU - McGarrity, Thomas

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AU - Nations, L.

AU - Lynch, P. M.

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AU - Frazier, M. L.

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N2 - Background and aims: Peutz-Jeghers syndrome (PJS) is a dominantly inherited disorder often caused by mutations in STK11. Time to onset of symptoms was characterised for a large collection of individuals with PJS who had been tested for STK11 mutations and genotype-phenotype correlations were evaluated. Methods: We characterised mutations in 42 independent probands and also used a historical cohort design to study 51 individuals with Peutz-Jeghers syndrome who had completed self-administered questionnaires. Results: Mutations were detected in 22/32 (69%) probands with PJS and 0/10 probands referred to rule out PJS. Real-time PCR analysis to quantitate DNA failed to detect any large deletions in PJS participants without STK11 mutations. The median time to onset for gastrointestinal symptoms or polypectomy was 13 years of age but showed a wide variability. Gastric polyps were frequent in PJS participants, with a median age at onset of 16 years. Individuals with missense mutations had a significantly later time to onset of first polypectomy (p=0.04) and of other symptoms compared with those participants either with truncating mutations or no detectable mutation. Conclusion: STK11 mutation analysis should be restricted to individuals who meet PJS criteria or their close relatives. Direct sequencing of STK11 yields a high rate of point mutations in individuals who meet phenotypic PJS criteria. Individuals with missense mutations of STK11 typically had a later time to onset for PJS symptoms. The common occurrence of gastric polyps may facilitate chemopreventive studies for this disorder.

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Amos CI, Keitheri-Cheteri MB, Sabripour M, Wei C, McGarrity T, Seldin MF et al. Genotype-phenotype correlations in Peutz-Jeghers syndrome. Journal of medical genetics. 2004 May 1;41(5):327-333.