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

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9302235 Publication Model: Print Cited Medium: Print ISSN: 1018-4813 (Print) Linking ISSN: 10184813 NLM ISO Abbreviation: Eur J Hum Genet Subsets: MEDLINE

Publication: <2003->: London : Nature Publishing Group
Original Publication: Basel ; New York : Karger, [1992-

Gene Deletion*; Peutz-Jeghers Syndrome/*genetics ; Protein Serine-Threonine Kinases/*genetics; AMP-Activated Protein Kinase Kinases ; Adolescent ; Adult ; Chromosomes, Human, Pair 19/genetics ; DNA/chemistry ; DNA/genetics ; DNA Mutational Analysis ; Exons/genetics ; Family Health ; Female ; Germ-Line Mutation ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Microsatellite Repeats ; Middle Aged ; Neurofibromatosis 1/genetics ; Neurofibromatosis 1/pathology ; Peutz-Jeghers Syndrome/pathology ; Polymerase Chain Reaction/methods

Peutz-Jeghers syndrome (PJS, MIM175200) is an autosomal-dominant inherited disorder characterised by multiple gastrointestinal hamartomatous polyps, melanin spots of the oral mucosa and digits, and an increased risk for various neoplasms. The PJS results from germline alterations of the STK11/LKB1 tumour suppressor gene, located on 19p13.3, and encoding a serine/threonine kinase. The detection of STK11 germline mutations, in only 50-70% of PJS families, has suggested a genetic heterogeneity of the disease. We report the case of a family with typical features of PJS, including gastrointestinal hamartomatous, breast cancers and melanin spots of the oral mucosa. Quantitative multiplex PCR of short fluorescent fragments (QMPSF) of the 19p13 region allowed us to identify an approximately 250 kb heterozygous deletion removing entirely the STK11 locus. 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 of STK11.

9007-49-2 (DNA)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
EC 2.7.11.1 (STK11 protein, human)
EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)

Date Created: 20040219 Date Completed: 20041102 Latest Revision: 20211203

20240829

10.1038/sj.ejhg.5201155

14970844