Investigation of Nagashima-type palmoplantar keratoderma in China: A cross-sectional study of 234 patients
Investigation of Nagashima-type palmoplantar keratoderma in China: A cross-sectional study of 234 patients
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中国长岛型掌跖角化症调查：234 例患者的横断面研究
DOI：
10.1111/1346-8138.16621
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发表时间：
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影响因子：
3.1
通讯作者：
Yang Y
中科院分区：
文献类型：
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作者：
Liu J;Chen Z;Hu L;Song Z;Mo R;Tsang LS;Liu Y;Huang X;Gong Z;Lin Z;Yang Y
长岛型掌跖角化病（NPPK）是中国最常见的遗传性掌跖角化病（PPK），但缺乏中国人群的流行病学数据。探讨NPPK的临床和遗传学特征，评估人口学分布，估计疾病负担。从两个医学中心和一个在线PPK支持小组共招募了234名中国NPPK患者。进行下一代测序和桑格测序以筛选并确认SERPINB 7中的致病性突变。使用自填问卷评价临床特征和生活质量（QOL）。在该队列中，总共在SERPINB 7中鉴定了14个致病性突变。前四位复发突变是c.796C>T（355，75.9%）、c.522dupT（66，14.1%）、c.650_653delCTGT（24，5.1%）和c.455G>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+ 2 T>G、c.635delG和7个新突变c.2T>C、c.434delG、c.455 - 16 A>G、c.656T>C、c.745 - 553 T>G、c.832C>T、c.1036G>T。根据中国数据库，中国NPPK的估计患病率为0.975/10 000。在临床上，NPPK患者没有明显的基因型-表型相关性。小儿以掌跖脱皮为主，成人以鳞屑为主（P< 0.001）。NPPK患者中最常见的合并症为甲真菌病（40.0%）、湿疹（36.8%）和手足癣（30.3%）。在疾病负担方面，NPPK患者的生活质量中度下降。本研究更新了SERPINB 7致病性突变的等位基因频率，并估计了中国NPPK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。发现新的突变对NPPK的及时诊断非常重要。儿童掌跖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 inSERPINB7. Clinical features and quality of life (QOL) were evaluated using self‐completed questionnaires. In total, 14 pathogenic mutations were identified inSERPINB7from 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 inSERPINB7were 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.