Peutz-Jeghers综合征致病基因的研究进展

Advances in causative genes for Peutz-Jeghers syndrome

Peutz-Jeghers综合征是一种较少见的常染色体显性遗传病，主要特点是皮肤黏膜的色素沉着及胃肠道多发息肉，并伴有高风险的胃肠道及胃肠道以外的恶性肿瘤，其发病机制尚未明确。Peutz-Jeghers综合征的人群发病率在1／8300-1／280000。目前多认为Peutz-Jeghers综合征的发生是由STKll（LKBl）基因突变所致，STKll基因编码的是一种丝氨酸，苏氨酸蛋白激酶，并通过调节细胞极性和功能作为一种抑癌基因普遍存在于各种类型的恶性肿瘤之中，该基因的抑癌机制尚未完全清楚。目前的研究表明可能存在其他相关致病基因，主要包括19q13．4区域可能基因、IFITMl基因及Brgl基因。

Peutz-Jeghers syndrome （PJS） is a rare autosomal dominant disorder characterized by mucocutaneous pigmentations and gastrointestinal polyposis associated with increased frequency of gastrointestinal and extraintestinal malignancies. The pathogenesis of PJS is unclear. The prevalence rate of PJS varies from 1/8 300 to 1/280 000. It is generally accepted that PJS is caused by germ-line mutations in the STKll （LKB1） gene that encodes the serine/threonine kinase and acts as a tumor suppressor by regulating cell polarity and functions in a variety of malignant tumors. The tumor-suppressing mechanism of STK11 gene is still not entirely understood. Present studies show that there may exist other causative genes for PJS, mainly including suspected loci at 19q13.4, fragile histidine triad （FHIT） gene, brahma-related gene 1 （Brgl）.