Human Genetics

, Volume 103, Issue 2, pp 168–172

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

  • Hidewaki Nakagawa
  • Kumiko Koyama
  • Yasuo Miyoshi
  • Hiroshi Ando
  • Shozo Baba
  • Masahiro Watatani
  • Masayuki Yasutomi
  • Nariaki Matsuura
  • Morito Monden
  • Y. Nakamura
Original Investigation

DOI: 10.1007/s004390050801

Cite this article as:
Nakagawa, H., Koyama, K., Miyoshi, Y. et al. Hum Genet (1998) 103: 168. doi:10.1007/s004390050801

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 families. One nonsense mutation and five different frameshift mutations (two families carried the same mutation), all of which would cause truncation of the gene product, were found in seven families; mutations found in five families were clustered within exon 6. Among these five mutations, three occurred at the mononucleotide-repeat region (CCCCCC) of codons 279–281, suggesting that this region is likely to be a mutational hotspot of this gene. One of the remaining three families carried a 3-bp in-frame deletion that would eliminate an asparagine residue within a kinase domain of the product; the other two carried intronic mutations at or adjacent to the consensus dinucleotide sequences of splice-acceptor or -donor sites, which were likely to lead to aberrant splicing.

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Hidewaki Nakagawa
    • 1
  • Kumiko Koyama
    • 1
  • Yasuo Miyoshi
    • 1
  • Hiroshi Ando
    • 2
  • Shozo Baba
    • 2
  • Masahiro Watatani
    • 3
  • Masayuki Yasutomi
    • 3
  • Nariaki Matsuura
    • 4
  • Morito Monden
    • 5
  • Y. Nakamura
    • 6
  1. 1.Department of Clinical Genetics, Biomedical Research Center, Osaka University, JapanJP
  2. 2.The 2nd Department of Surgery, Hamamatsu University Medical School, JapanJP
  3. 3.The 1st Department of Surgery, Kinki University, JapanJP
  4. 4.Department of Pathology, School of Allied Health Sciences, Faculty of Medicine, Osaka University Medical School, JapanJP
  5. 5.The 2nd Department of Surgery, Osaka University Medical School, JapanJP
  6. 6.Laboratory Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato, Tokyo 108-8639, Japan e-mail: yusuke@ims.u.-tokyo.ac.jp, Tel.: +81-3-5449-5372, Fax: +81-3-5449-5433JP

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