先天性白甲(PC)是一组由五种角蛋白基因之一的突变引起的常染色体显性疾病(KRT6A,KRT6B,KRT6C,KRT16、KRT17)。包含临床和分子数据的国际注册中心的建立导致了基于突变基因和相关特征的疾病分类的发展。
为了利用相同的资源来阐明PC相关临床特征的患病率,描述表型-基因型相关性并确定疾病严重程度的预后特征。
总共,对815名在国际白甲菌研究登记处注册的已确认角蛋白突变的个体进行了与PC相关的临床发现调查。使用各种统计方法分析数据,包括学生t检验,均值/比例差异的χ2检验和方差分析。Spearman相关和逻辑回归用于表型-基因型相关性。
KRT6A突变与口腔白质角化病相关,声音嘶哑,涉及的指甲/脚趾甲年龄最小或数量最多,和使用助行器。KRT17突变最常与囊肿和出生牙齿相关。使用逻辑回归,我们发现口腔白质角化病与较早的趾甲受累有关,助行器,护理困难和声音嘶哑。囊肿与口腔白质角化病相关,出生时的牙齿和耳垢。Natal牙齿预测了较早的脚趾甲受累,行走困难和囊肿形成。声音嘶哑与涉及的指甲数量增加有关。
这里,我们在迄今为止描述的最大的PC患者队列中建立了表型-基因型相关性,并揭示了新的和临床上有用的病程和表现预测因子.关于这个主题已经知道了什么?先天性灰甲(PC)是一组由五个角蛋白基因之一的突变引起的常染色体显性疾病(KRT6A,KRT6B,KRT6C,KRT16、KRT17)。主要临床特征是指甲营养不良,掌plant角化病,口腔白质角化病和囊肿。包含PC患者临床和分子数据的国际注册中心的建立导致了基于突变基因和相关特征的疾病分类的发展。这项研究增加了什么?数据是通过国际注册中心收集的,以阐明与PC相关的临床特征的患病率。描述表型-基因型相关性并确定疾病严重程度的预后特征。这是迄今为止描述的最大的PC患者队列。PC的最早临床表现是指甲营养不良和掌足底角化病。在学龄前可以怀疑和确认诊断。痛性足底角化症对生活质量和日常功能具有最深刻和最衰弱的影响。链接社论:斯蒂尔和奥图尔。BrJDermatol2020;182:521-522。链接评论:Mordaunt。BrJDermatol2020;182:537。
Pachyonychia congenita (PC) is a group of autosomal dominant disorders caused by mutations in one of five keratin genes (KRT6A, KRT6B, KRT6C, KRT16, KRT17). The establishment of an international registry containing clinical and molecular data led to the development of a disease classification based on the mutant gene and associated features.
To harness the same resource to clarify the prevalence of PC-associated clinical features, delineate phenotype-genotype correlations and identify prognostic features for disease severity.
In total, 815 individuals with confirmed keratin mutations registered in the International Pachyonychia Congenita Research Registry were surveyed for clinical findings associated with PC. Data were analysed using various statistical methods, including the Student\'s t-test, χ2 -test and anova tests for differences in means/proportions. Spearman correlation and logistic regression were used for phenotype-genotype correlations.
KRT6A mutations were associated with oral leucokeratosis, hoarseness, youngest age or highest number of fingernails/toenails involved, and use of walking aids. KRT17 mutations were most commonly associated with cysts and natal teeth. Using logistic regression, we found that oral leucokeratosis was correlated with earlier toenail involvement, walking aids, nursing difficulties and hoarseness. Cysts were correlated with oral leucokeratosis, natal teeth and ear wax. Natal teeth predicted earlier toenail involvement, walking difficulties and cyst formation. Hoarseness was correlated with an increased number of involved fingernails.
Here, we establish phenotype-genotype correlations in the largest cohort of patients with PC described to date and reveal novel and clinically useful predictors of disease course and manifestations. What\'s already known about this topic? Pachyonychia congenita (PC) is a group of autosomal dominant disorders caused by mutations in one of five keratin genes (KRT6A, KRT6B, KRT6C, KRT16, KRT17). The main clinical features are nail dystrophy, palmoplantar keratoderma, oral leucokeratosis and cysts. The establishment of an international registry containing the clinical and molecular data of patients with PC led to the development of a disease classification based on the mutant gene and associated features. What does this study add? Data were collected via an international registry to clarify the prevalence of PC-associated clinical features, delineate phenotype-genotype correlations and identify prognostic features for disease severity. This is the largest cohort of patients with PC described to date. The earliest clinical manifestations of PC are nail dystrophy and palmoplantar keratoderma. Diagnosis can be suspected and confirmed in preschool years. Painful plantar keratoderma has the most profound and debilitating effect on quality of life and daily function. Linked Editorial: Steele and O\'Toole. Br J Dermatol 2020; 182:521-522. Linked Comment: Mordaunt. Br J Dermatol 2020; 182:537.