Introduction Porokeratosis is a rare chronic progressive hypokeratotic skin disease, possibly related to the mevalonate pathway. Variations in four enzymes, including phosphomevalonate kinase (PMVK) may alter this pathway, ultimately leading to porokeratosis. Methods In this study, Sanger sequencing was used to identify the gene variant causative of porokeratosis; its population frequency was investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in four patients and three normal individuals as well as in 100 normal unrelated controls; finally, the pathogenicity of the mutation and the associated structural changes were predicted. Results We identified a novel heterozygous missense variant, c.207G>T (p. Lys69Asn) in the PMVK gene. This variant was found in all patients but not in the normal individuals in this family or in the 100 controls. In silico analysis indicated that the variant was pathogenic; p.Lys69Asn changed the length of the α-helix and the hydrogen bond pattern compared with the wild type protein. Discussion/Conclusion The novel variant c.207G>T (p. Lys69Asn) in the PMVK gene was the causative variant in this porokeratosis family. This finding provides further evidence for the genetic basis of this disease.

中文翻译：

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一种与家族性汗孔角化症相关的新型 PMVK 变体。

引言 汗孔角化病是一种罕见的慢性进行性角化不足性皮肤病，可能与甲羟戊酸途径有关。四种酶的变化，包括磷酸甲羟戊酸激酶 (PMVK)，可能会改变这一途径，最终导致汗孔角化症。方法本研究采用Sanger测序法鉴定导致汗孔角化症的基因变异；通过聚合酶链反应-限制性片段长度多态性 (PCR-RFLP) 在 4 名患者和 3 名正常个体以及 100 名正常无关对照中调查其群体频率；最后，预测了突变的致病性和相关的结构变化。结果 我们在 PMVK 基因中发现了一个新的杂合错义变异 c.207G>T (p. Lys69Asn)。这种变异在所有患者中均有发现，但在该家族的正常个体或 100 名对照者中均未发现。计算机分析表明该变异具有致病性；与野生型蛋白相比，p.Lys69Asn 改变了 α-螺旋的长度和氢键模式。讨论/结论 PMVK 基因中的新变异 c.207G>T (p. Lys69Asn) 是该汗孔角化症家族的致病变异。这一发现为这种疾病的遗传基础提供了进一步的证据。