Le Meur Nathalie, Martin Cosette, Saugier-Veber Pascale, Joly Géraldine, Lemoine Françoise, Moirot Hélène, Rossi Annick, Bachy Bruno, Cabot Annick, Joly Pascal, Frébourg Thierry
Department of Genetics, CHU of Rouen, France.
Eur J Hum Genet. 2004 May;12(5):415-8. doi: 10.1038/sj.ejhg.5201155.
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.
黑斑息肉综合征（PJS，MIM175200）是一种常染色体显性遗传性疾病，其特征为多发胃肠道错构瘤性息肉、口腔黏膜和指（趾）部的黑色素斑，以及患多种肿瘤的风险增加。PJS是由位于19p13.3的STK11/LKB1肿瘤抑制基因的种系改变引起的，该基因编码一种丝氨酸/苏氨酸激酶。仅在50%-70%的PJS家族中检测到STK11种系突变，这表明该疾病存在遗传异质性。我们报告了一个具有PJS典型特征的家族病例，包括胃肠道错构瘤、乳腺癌和口腔黏膜黑色素斑。对19p13区域的短荧光片段进行定量多重PCR（QMPSF），使我们能够鉴定出一个约250 kb的杂合缺失，该缺失完全去除了STK11基因座。本报告首次描述了STK11的完整种系缺失，表明在未检测到STK11点突变的PJS家族中应考虑存在此类大的基因组缺失。
