长岛型掌底角化病(NPPK)是中国最常见的遗传性掌底角化病,但是中国人口的流行病学数据很少。探讨临床及遗传特点,评估人口分布,并估计NPPK的疾病负担。来自两个医疗中心和一个在线PPK支持小组的234名中国NPPK患者被纳入。进行下一代测序和Sanger测序以筛选并确认SERPINB7中的致病性突变。使用自填问卷评估临床特征和生活质量(QOL)。总的来说,在来自队列的SERPINB7中鉴定出14个致病性突变。前四个复发突变为c.796C>T(355,75.9%),c.522dupT(66,14.1%),c.650_653delCTGT(24,5.1%),和c.45.5G>T(12,2.6%),占中国NPPK患者的97.6%。其他突变(11,2.4%)包括c.455-1G>T,c.336+2T>G,c.635delG和七个新突变c.2T>C,c.434delG,c.455-16A>G,c.656T>C,c.745-553T>G,c.832C>T,c.1036G>T.根据中国数据库,估计NPPK在中国的患病率为0.975/10000。临床上,NPPK患者没有明显的基因型-表型相关性.小儿患者主要表现为掌足底脱皮,而成人呈现量表(p<0.001)。NPPK患者最常见的合并症是甲癣(40.0%),湿疹(36.8%),和足癣(30.3%)。至于疾病负担,NPPK患者的生活质量中度下降。在这项研究中,SERPINB7的致病突变等位基因频率被更新,并估计了NPPK在中国的患病率。这项大规模队列研究为患者管理提供了基于证据的建议。新突变的鉴定对于NPPK的及时诊断很重要。儿童掌足底脱皮可作为早期识别NPPK的标志。
Nagashima-type palmoplantar keratoderma (NPPK) is the most prevalent hereditary palmoplantar keratoderma (PPK) in China, but there is a paucity of epidemiological data on the Chinese population. To explore the clinical and genetic characteristics, evaluate the demographic distribution, and estimate the burden of disease of NPPK. A total of 234 Chinese patients with NPPK were enrolled from two medical centers and an online PPK support group. Next-generation sequencing and Sanger sequencing were performed to screen out and confirm pathogenic mutations in SERPINB7. Clinical features and quality of life (QOL) were evaluated using self-completed questionnaires. In total, 14 pathogenic mutations were identified in SERPINB7 from the cohort. The top four recurrent mutations were c.796C>T (355, 75.9%), c.522dupT (66, 14.1%), c.650_653delCTGT (24, 5.1%), and c.455G>T (12, 2.6%), accounting for 97.6% of Chinese NPPK patients. Other mutations (11, 2.4%) include c.455-1G>T, c.336+2T>G, c.635delG and seven novel mutations c.2T>C, c.434delG, c.455-16A>G, c.656T>C, c.745-553T>G, c.832C>T, c.1036G>T. The estimated prevalence of NPPK in China was found to be 0.975/10 000 based on Chinese databases. Clinically, there were no apparent genotype-phenotype correlations in NPPK patients. Pediatric patients mainly presented with palmoplantar peeling, while adults presented with scale (p < 0.001). The most common comorbidities in NPPK patients were onychomycosis (40.0%), eczema (36.8%), and tinea pedis (30.3%). As for burden of disease, NPPK patients\' QOL was decreased by a moderate degree. In this study, pathogenic mutations\' allele frequencies in SERPINB7 were updated, and prevalence of NPPK in China was estimated. This large-scale cohort study provides evidence-based recommendations for patient management. Identification of new mutations are important for timely diagnosis of NPPK. Palmoplantar peeling in children can be used as a hallmark for early recognition of NPPK.