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Peutz-Jeghers Syndrome: Confirmation of Linkage to Chromosome 19p13.3 and Identification of a Potential Second Locus, on 19q13.4
Authors:Hamid Mehenni  Jean-Louis Blouin  Uppala Radhakrishna  Shiv Shanker Bhardwaj  Kamla Bhardwaj  V.B. Dixit  Kent F. Richards  Ambrosio Bermejo-Fenoll  Antonio Silva Leal  Ranjan C. Raval  Stylianos E. Antonarakis
Affiliation:1Laboratory of Human Molecular Genetics, Department of Genetics and Microbiology, Geneva University Medical School, and Division of Medical Genetics, Cantonal Hospital, Geneva;2Government General Hospital, Bhiwani, India;3University Hospital of Utah Medical Center, Salt lake City;4Catedratico de Medicina Bucal, Universidad de Murcia, Murcia, Spain;5Department of Surgery, University of Porto, Porto, Portugal;6Department of Dermatology, Civil Hospital and Medical College, Ahmedabad, India
Abstract:Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease with variable expression and incomplete penetrance, characterized by mucocutaneous pigmentation and hamartomatous polyposis. Patients with PJS have increased frequency of gastrointestinal and extraintestinal malignancies (ovaries, testes, and breast). In order to map the locus (or loci) associated with PJS, we performed a genomewide linkage analysis, using DNA polymorphisms in six families (two from Spain, two from India, one from the United States, and one from Portugal) comprising a total of 93 individuals, including 39 affected and 48 unaffected individuals and 6 individuals with unknown status. During this study, localization of a PJS gene to 19p13.3 (around marker D19S886) had been reported elsewhere. For our families, marker D19S886 yielded a maximum LOD score of 4.74 at a recombination fraction (theta) of .045; multipoint linkage analysis resulted in a LOD score of 7.51 for the interval between D19S886 and 19 pter. However, markers on 19q13.4 also showed significant evidence for linkage. For example, D19S880 resulted in a maximum LOD score of 3.8 at theta = .13. Most of this positive linkage was contributed by a single family, PJS07. These results confirm the mapping of a common PJS locus on 19p13.3 but also suggest the existence, in a minority of families, of a potential second PJS locus, on 19q13.4. Positional cloning and characterization of the PJS mutations will clarify the genetics of the syndrome and the implication of the gene(s) in the predisposition to neoplasias.
Keywords:Author Keywords: Peutz-Jeghers syndrome   Chromosome 19   Linkage analysis   Neoplasias   Cancer, intestinal
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