Familial Cancer

, Volume 16, Issue 3, pp 417–422 | Cite as

A lesson from a reported pathogenic variant in Peutz-Jeghers syndrome: a case report

  • Hu Tan
  • Xianda Wei
  • Pu Yang
  • Yanru Huang
  • Haoxian Li
  • Desheng Liang
  • Lingqian WuEmail author
Short Communication


Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterized by mucocutaneous hyperpigmentation, gastrointestinal (GI) hamartmatous polyps, and an increased risk of various malignancies. Pathogenic variants in the LKB1 tumor suppressor gene (also known as STK11) are the major cause of PJS. In this study, compound heterozygous variants of LKB1, c.890G > A/ c.1062C > G and del(exon1)/ c.1062C > G, were identified in two sporadic Chinese PJS cases respectively. Although all these three variants had been related to the autosomal dominant PJS in previous studies, all evidences collected in this study including de novo data, segregation data, population data, in-silico data, and functional data indicated that del(exon1) and c.890G > A are pathogenic in these two PJS families rather than c.1062C > G. This finding would contribute to genetic counseling for individuals carrying the variant c.1062C > G with or without PJS phenotypes. Moreover, this finding reminds genetic counselors that it is necessary to reevaluate the pathogenicity of reported variants in a known Mendelian disorder in order to avoid a misleading decision.


Peutz-Jeghers syndrome LKB1 Variant Pathogenicity Genetic counseling 



The authors are thankful for the participation of the patients, their families, their clinicians and volunteers in this study. This study was supported by grants from the National Key Basic Research Program of China (2012CB944600), the National Natural Science Foundation of China (81270706) and The National Key Technology R&D Program of China (2012BAI09B05).

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Supplementary material

10689_2016_9963_MOESM1_ESM.tif (1.8 mb)
Cosegregation analysis in the PJS families. (A) Variant c.890G>A was de novo in family 1. (B) Variant c.1062C>G was paternal in family 1. (C) Variant c.1062C>G was paternal in family 2. (D) Variant del(exon1) was de novo in family 2. Arrows indicate the variant sites. (TIF 1794 KB)
10689_2016_9963_MOESM2_ESM.docx (13 kb)
Supplementary material 2 (DOCX 13 KB)


  1. 1.
    Giardiello FM, Trimbath JD (2006) Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol 4(4):408–415CrossRefPubMedGoogle Scholar
  2. 2.
    Jenne DE, Reimann H, Nezu J et al (1998) Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 18(1):38–43CrossRefPubMedGoogle Scholar
  3. 3.
    Volikos E, Robinson J, Aittomaki K et al (2006) LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers syndrome. J Med Genet 43(5):e18CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Amos CI, Keitheri-Cheteri MB, Sabripour M et al (2004) Genotype-phenotype correlations in Peutz-Jeghers syndrome. J Med Genet 41(5):327–333CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Yajima H, Isomoto H, Nishioka H et al (2013) Novel serine/threonine kinase 11 gene mutations in Peutz-Jeghers syndrome patients and endoscopic management. World J Gastrointest Endosc 5(3):102–110CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Dai L, Fu L, Liu D et al (2014) Novel and recurrent mutations of STK11 gene in six Chinese cases with Peutz-Jeghers syndrome. Dig Dis Sci 59(8):1856–1861CrossRefPubMedGoogle Scholar
  7. 7.
    Westerman AM, Entius MM, Boor PP et al (1999) Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families. Hum Mutat 13(6):476–481CrossRefPubMedGoogle Scholar
  8. 8.
    Mehenni H, Gehrig C, Nezu J et al (1998) Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity. Am J Hum Genet 63(6):1641–1650CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Zeqiraj E, Filippi BM, Deak M, Alessi DR, van Aalten DM (2009) Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation. Science 326(5960):1707–1711CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Wang Z, Wu B, Mosig RA et al (2014) STK11 domain XI mutations: candidate genetic drivers leading to the development of dysplastic polyps in Peutz-Jeghers syndrome. Hum Mutat 35(7):851–858CrossRefPubMedGoogle Scholar
  12. 12.
    Morton JP, Jamieson NB, Karim SA, et al (2010) LKB1 haploinsufficiency cooperates with Kras to promote pancreatic cancer through suppression of p21-dependent growth arrest. Gastroenterology 139(2):586–97, 591–7CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Miyoshi H, Nakau M, Ishikawa TO, Seldin MF, Oshima M, Taketo MM (2002) Gastrointestinal hamartomatous polyposis in Lkb1 heterozygous knockout mice. Cancer Res 62(8):2261–2266PubMedGoogle Scholar
  14. 14.
    Salloch H, Reinacher-Schick A, Schulmann K et al (2010) Truncating mutations in Peutz-Jeghers syndrome are associated with more polyps, surgical interventions and cancers. Int J Colorectal Dis 25(1):97–107CrossRefPubMedGoogle Scholar
  15. 15.
    Masuda K, Kobayashi Y, Kimura T, et al (2016) Characterization of the STK11 splicing variant as a normal splicing isomer in a patient with Peutz-Jeghers syndrome harboring genomic deletion of the STK11 gene. Hum Genome Var 3:16002CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Beggs AD, Latchford AR, Vasen HF et al (2010) Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut 59(7):975–986CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.The State Key Laboratory of Medical GeneticsCentral South UniversityChangshaChina
  2. 2.Hunan Jiahui Genetics HospitalChangshaChina

Personalised recommendations