Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers syndrome

  title={Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers syndrome},
  author={Hidewaki Nakagawa and Kumiko Koyama and Yasuo Miyoshi and Hiroshi Ando and Shozo Baba and Masahiro Watatani and Masayuki Yasutomi and Nariaki Matsuura and Morito Monden and Y Nakamura},
  journal={Human Genetics},
Abstract Peutz-Jeghers Syndrome (PJS) is an autosomal dominant hereditary disease characterized by hamartomatous polyposis involving the entire bowel. Recently STK11, a gene bearing a mutation responsible for PJS, was isolated. We investigated the entire coding region of STK11 in 15 unrelated PJS families by the PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) method and PCR-direct sequence analysis, and found nine different, novel mutations among ten of those… 

Mutations analysis ofSTK11 gene in Chinese families with Peutz-Jeghers syndrome

Mutation frequency is higher in the families suffering PJS in three or more generations than that of the sporadic cases, indicating that the point mutation inSTK11 might be involved in PJS patho-genesis.

Germline mutations of the STK11 gene in Korean Peutz–Jeghers syndrome patients

Findings indicate that germline mis-sense mutations of the STK11 gene are found in PJS patients in addition to truncating mutations, and the effects of these mutations on protein function require further examination.

Germline mutations of the LKB1 (STK11) gene in Peutz-Jeghers patients

P predictive and diagnostic testing for LKB1 mutations will be useful for selected patients in both familial and non-familial contexts, despite the fact that Peutz-Jeghers syndrome is usually an early onset disease with characteristic clinical features.

A De Novo Mutation of STK11 Gene in a Chinese Patient with Peutz–Jeghers Syndrome

The results presented here enlarge the spectrum of mutations of the STK11 gene by identifying a de novo mutation in a PJS patient and further support the hypothesis that STK 11 mutations are disease-causing mutations for PJS.

LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers syndrome

These results lessen the possibility of a second PJS locus, as the detection rate of germline mutations in PJS patients was about 80% (59/76), and it is suggested that MLPA, or a suitable alternative, should be used for routine genetic testing of P JS patients in clinical practice.

Complete germline deletion of the STK11 gene in a family with Peutz–Jeghers syndrome

This report, which constitutes the first description of a complete germline deletion of STK11, shows that the presence of such large genomic deletions should be considered in PJS families without detectable point mutations ofSTK11.

High proportion of large genomic STK11 deletions in Peutz‐Jeghers syndrome

Screening for point mutations and large deletions by direct sequencing or MLPA increased the mutation detection rate in the STK11 gene up to 94% and it is questionable whether a second PJS locus exists at all.

Mutations in the human LKB1/STK11 gene

A review of the literature provides a total of 40 different somatic LKB1 mutations in 41 sporadic tumors and seven cancer cell lines, which are concordant with the germline mutation spectrum.

Genetic heterogeneity in Peutz‐Jeghers syndrome

Mutation analysis revealed genetic alterations in LKB1 in two probands who had a family history of PJS, suggesting the presence of significant genetic heterogeneity for PJS and the involvement of other loci in this syndrome.

De novo germline mutation in the serine–threonine kinase STK11/LKB1 gene associated with Peutz–Jeghers syndrome

DNA from microdissected gastrointestinal hamartomatous polyps in the PJS patient was isolated and the loss of heterozygosity (LOH) at the LKB1 locus was investigated by real‐time fluorescence polymerase chain reaction genotyping using a fluorescent resonance energy transfer technique, suggesting a different mechanism from LOH in the formation of hamarto- polyps.



Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase.

It is concluded that germline mutations in STK11, probably in conjunction with acquired genetic defects of the second allele in somatic cells, cause the manifestations of PJ syndrome.

Peutz-Jeghers syndrome: confirmation of linkage to chromosome 19p13.3 and identification of a potential second locus, on 19q13.4.

Results confirm the mapping of a common P JS locus on 19p13.3 but also suggest the existence, in a minority of families, of a potential second PJS locus, on 19q13.4.

Localization of the gene responsible for Peutz-Jeghers syndrome within a 6-cM region of chromosome 19p13.3

Using microsatellite markers on chromosome 19p, the region containing the gene responsible for Peutz-Jeghers syndrome is closely defined through linkage analysis in seven affected families, confirming the localization of the PJS locus to chromosome 19.

A serine/threonine kinase gene defective in Peutz–Jeghers syndrome

The molecular background of the Peutz–Jeghers syndrome, a rare hereditary disease in which there is predisposition to benign and malignant tumours of many organ systems, is investigated and truncating germline mutations in a gene residing on chromosome 19p are identified.

Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis

A search for a putative tumour suppressor locus was made using comparative genomic hybridization of Peutz-Jeghers polyps, combined with loss of heterozygosity (LOH), and molecular evidence of malignant potential in hamartomas is provided.

Fine mapping of a genetic locus for Peutz-Jeghers syndrome on chromosome 19p.

It is found that all carriers expressed the PJS phenotype and no noncarriers displayed PJS sequellae, indicating complete penetrance with no sporadic cases, and no evidence for genetic heterogeneity is found.

Increased risk of cancer in the Peutz-Jeghers syndrome.

It is suggested that patients with the Peutz-Jeghers syndrome have an increased risk for the development of cancer at gastrointestinal and nongastrointestinal sites.

The Peutz-Jeghers syndrome. Is there a predisposition to the development of intestinal malignancy?

Isolated reports of apparent gastrointestinal tract malignancies in patients with the PeutzJeghers syndrome have stimulated further thought on the interpretation of evidence and, therefore, the proper treatment of the patients.

Cancer and the Peutz-Jeghers syndrome.

There is evidence for a hamartoma/carcinoma sequence in the Peutz-Jeghers syndrome, suggesting that the gene locus involved is relevant to the development of malignancy in general.

Neoplastic transformation arising in Peutz-Jeghers polyposis

Neoplastic transformation is not a rare event, and the results may indicate evidence of a hamartoma-adenoma-carcinoma sequence in Peutz-Jeghers polyposis.