Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Clin Exp Dermatol. 2021 Jun;46(4):663-668. doi: 10.1111/ced.14509. Epub 2020 Dec 20.
Pachyonychia congenita (PC) is a rare autosomal dominant disorder featuring palmoplantar keratoderma, nail dystrophy, oral leucokeratosis, pilosebaceous cysts and natal teeth. PC results from dominant mutations in one of five genes (KRT6A, KRT6B, KRT6C, KRT16, KRT17) encoding keratin proteins.
To delineate the clinical and genetic features of PC in a series of Israeli patients.
We used direct sequencing of genomic DNA, and also used cDNA sequencing where applicable.
We collected clinical information and molecular data in a cohort of Israeli families diagnosed with PC (n = 16). Most of the patients were Ashkenazi Jews and had a family history of PC. The most common clinical findings were painful focal plantar keratoderma (94%) accompanied by nail dystrophy (81%), pilosebaceous cysts (31%) and prenatal/natal teeth (13%). In contrast to the high prevalence of KRT6A mutations in other populations, we found that KRT16 mutations were the most common type among Israeli patients with PC (56%). Most (77%) of the Israeli patients with PC with KRT16 mutation carried the same variant (c.380G>A; p.R127H) and shared the same haplotype around the KRT16 locus, suggestive of a founder effect.
The data gleaned from this study emphasizes the importance of population-specific tailored diagnostic strategies.
先天性厚甲症（PC）是一种罕见的常染色体显性遗传疾病，其特征为掌跖角化过度、甲营养不良、口腔白色角化病、毳毛皮脂腺囊肿和出生牙。PC 是由编码角蛋白蛋白的五个基因（KRT6A、KRT6B、KRT6C、KRT16、KRT17）中的一个显性突变引起的。
阐明一系列以色列患者中 PC 的临床和遗传特征。
我们使用基因组 DNA 的直接测序，以及在适用的情况下使用 cDNA 测序。
我们收集了以色列被诊断为 PC 的家族的临床信息和分子数据（n=16）。大多数患者为阿什肯纳兹犹太人，有 PC 的家族史。最常见的临床发现是疼痛性局灶性足底角化过度（94%），伴有甲营养不良（81%）、毳毛皮脂腺囊肿（31%）和出生前/出生牙（13%）。与其他人群中 KRT6A 突变的高发生率相比，我们发现 KRT16 突变是以色列 PC 患者中最常见的类型（56%）。大多数（77%）以色列 KRT16 突变型 PC 患者携带相同的变体（c.380G>A；p.R127H），并在 KRT16 基因座周围共享相同的单倍型，提示存在一个奠基者效应。
本研究的数据强调了针对特定人群的定制诊断策略的重要性。
