Risk J M, Ruhrberg C, Hennies H, Mills H S, Di Colandrea T, Evans K E, Ellis A, Watt F M, Bishop D T, Spurr N K, Stevens H P, Leigh I M, Reis A, Kelsell D P, Field J K
Department of Clinical Dental Sciences, The University of Liverpool, Liverpool, L69 3BX, United Kingdom.
Genomics. 1999 Jul 15;59(2):234-42. doi: 10.1006/geno.1999.5857.
Focal nonepidermolytic palmoplantar keratoderma (NEPPK), or tylosis, is an autosomal, dominantly inherited disorder of the skin that manifests as focal thickening of the palmar and plantar surfaces. In three families studied, the skin disorder cosegregates with esophageal cancer and oral lesions. New haplotype analysis, presented here, places the tylosis esophageal cancer (TOC) locus between D17S1839 and D17S785. Envoplakin (EVPL) is a protein component of desmosomes and the cornified envelope that is expressed in epidermal and esophageal keratinocytes and has been localized to the TOC region. Mutation analysis of EVPL in the three affected families failed to show tylosis-specific mutations, and haplotype analysis of three intragenic sequence polymorphisms of the EVPL gene placed it proximal to D17S1839. Confirmation of the exclusion of EVPL as the TOC gene by location was obtained by integration of the genetic and physical mapping data using radiation hybrid, YAC, BAC, and PAC clones. This new physical map will allow further identification of candidate genes underlying NEPPK associated with esophageal cancer, which may also be implicated in the development of sporadic squamous cell esophageal carcinoma and Barrett's adenocarcinoma.
局灶性非表皮松解性掌跖角化病（NEPPK），即胼胝形成，是一种常染色体显性遗传性皮肤病，表现为手掌和足底表面的局灶性增厚。在研究的三个家族中，这种皮肤病与食管癌和口腔病变共分离。本文提出的新单倍型分析将胼胝形成 - 食管癌（TOC）基因座定位在D17S1839和D17S785之间。桥粒斑蛋白（EVPL）是桥粒和角质化包膜的一种蛋白质成分，在表皮和食管角质形成细胞中表达，并已定位到TOC区域。对三个受累家族的EVPL进行突变分析未能显示出胼胝形成特异性突变，对EVPL基因的三个基因内序列多态性进行单倍型分析将其定位在D17S1839近端。通过使用辐射杂种、酵母人工染色体（YAC）、细菌人工染色体（BAC）和P1人工染色体（PAC）克隆整合遗传和物理图谱数据，从位置上证实了排除EVPL作为TOC基因。这种新的物理图谱将有助于进一步鉴定与食管癌相关的NEPPK潜在候选基因，这些基因也可能与散发性鳞状细胞食管癌和巴雷特腺癌的发生有关。
