Hereditary Leukonychia, or Porcelain Nails, Resulting from Mutations in PLCD1
Hereditary Leukonychia, or Porcelain Nails, Resulting from Mutations in PLCD1
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DOI：
10.1016/j.ajhg.2011.05.014
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发表时间：
2011-06-10
影响因子：
9.8
通讯作者：
Christiano, Angela M.
中科院分区：
文献类型：
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作者：
Kiuru, Maija;Kurban, Mazen;Christiano, Angela M.
遗传性白甲病（瓷甲或白甲）是一种罕见的指甲疾病，其遗传基础未知。为了鉴定这种表型背后的基因变异，我们鉴定了四个巴基斯坦血统的家族，它们表现出遗传性白甲病的特征。每个受影响个体的所有 20 个指甲外观都是白垩色和白色，与全白甲一致，没有其他皮肤、附件或全身发现。通过使用 Affymetrix 10K 芯片，我们建立了与染色体 3p21.3-p22 的连锁，LOD 得分 (Z) 为 5.1。我们在所有四个家族中都鉴定出了 PLCD1 的致病性突变，该家族编码磷酸肌醇特异性磷脂酶 C delta 1 亚基，这是磷酸肌醇代谢中的关键酶。然后我们确定了 PLCD1 在指甲基质中的定位。最近通过蛋白质组学分析表明，PLCD1是人类指甲板的组成部分，并且定位于人类指甲的基质中。此外，PLCD1 中检测到的突变导致体外酶活性降低。我们的数据表明，PLCD1 的突变是遗传性白甲病的基础，揭示了参与指甲生长分子控制的基因。
Hereditary leukonychia (porcelain nails or white nails) is a rare nail disorder with an unknown genetic basis. To identify variants in a gene underlying this phenotype, we identified four families of Pakistani origin showing features of hereditary leukonychia. All 20 nails of each affected individual were chalky and white in appearance, consistent with total leukonychia, with no other cutaneous, appendageal, or systemic findings. By using Affymetrix 10K chip, we established linkage to chromosome 3p21.3-p22 with a LOD score (Z) of 5.1. We identified pathogenic mutations in PLCD1 in all four families, which encodes phosphoinositide-specific phospholipase C delta 1 subunit, a key enzyme in phosphoinositide metabolism. We then identified localization of PLCD1 in the nail matrix. It was recently shown that PLCD1 is a component of the human nail plate by proteomic analysis and is localized in the matrix of human nails. Furthermore, mutations detected in PLCD1 resulted in reduced enzymatic activity in vitro. Our data show that mutations in PLCD1 underlie hereditary leukonychia, revealing a gene involved in molecular control of nail growth.