PDF(Pubmed)
Abstract：
Pachyonychia congenita (PC) is a group of rare hereditary disorders, characterised by hypertrophic nails and palmoplantar keratoderma (PPK), particularly localised to the pressure areas of the feet. At a molecular level, it is caused by mutations in genes encoding KRT6A, KRT6B, KRT6C, KRT16, or KRT17. To identify the underlying gene mutation in a Chinese family with PC presenting with disabling palmoplantar keratoderma and subsequent associated acral melanoma. Genomic DNA was extracted from peripheral blood samples of three available individuals in the Chinese family, which included the patient and his two unaffected sisters. The index patient presented with severe palmoplantar keratoderma as well as a newly diagnosed acral malignant melanoma (MM). Whole-exome sequencing (WES) was carried out with amplification of exon 1 of KRT16 by polymerase chain reaction (PCR). PCR products were then sequenced to identify potential mutations. We identified the proline substitution mutation p.Arg127Pro (c.380G>C) in our patient\'s 1A domain of KRT16. The same mutation was not found in his sisters or unrelated healthy controls. The mutation (p.Arg127Pro (c.380G>C)) in KRT16 has been reported in Dutch patients with PC. However, it is the first such report of a patient with a PC of Chinese origin. In addition, the acral MM occurred under the background of genetic PPK caused by KRT16 mutation in this patient.
摘要：
先天性甲癣（PC）是一组罕见的遗传性疾病，以肥厚性指甲和掌plant角化病（PPK）为特征，特别局限于脚的压力区域。在分子水平上,它是由编码KRT6A的基因突变引起的，KRT6B,KRT6C,KRT16或KRT17。目的鉴定一个中国家族的PC患者中潜在的基因突变，该家族表现为致残的掌plant角质病和随后的相关肢端黑色素瘤。基因组DNA是从中国家庭中三个可用个体的外周血样本中提取的，其中包括病人和他的两个未受影响的姐妹。该指标患者患有严重的掌plant角化病以及新诊断的肢端恶性黑色素瘤（MM）。通过聚合酶链反应（PCR）扩增KRT16的外显子1，进行全外显子组测序（WES）。然后对PCR产物进行测序以鉴定潜在的突变。我们在我们患者的KRT16的1A结构域中鉴定了脯氨酸取代突变p.Arg127Pro(c.380G>C)。在他的姐妹或无关的健康对照中未发现相同的突变。突变（p。在荷兰的PC患者中已经报道了KRT16中的Arg127Pro（c.380G>C）。然而,这是第一份中国血统的PC患者的此类报告。此外,该患者的肢端MM是在KRT16突变引起的遗传PPK背景下发生的。
