Mutations in the mevalonate pathway genes in Chinese patients with porokeratosis
Mutations in the mevalonate pathway genes in Chinese patients with porokeratosis
复制标题
中国汗孔角化症患者甲羟戊酸途径基因突变
DOI：
10.1111/jdv.13653
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发表时间：
2016-09-01
影响因子：
9.2
通讯作者：
Yao, Z.
中科院分区：
文献类型：
--
作者：
Li, M.;Li, Z.;Yao, Z.
背景：角化孔症（PK, MIM 175800）是一种慢性常染色体显性皮肤角化疾病，具有多种临床表现。目的分析中国人群中不同亚型的10个家族和12例散发性角化症的分子基础。方法提取小鼠外周血基因组DNA。通过对四个甲羟戊酸途径基因和SLC17A9基因的整个编码区外显子和侧边内含子-外显子边界的直接测序进行突变筛选。结果通过PCR产物的直接序列分析，检测到3个新突变和7个先前描述的突变。甲基戊酸脱羧酶（MVD）的p.Phe249Ser和p.p asn292ser突变是该PK队列中最常见的突变；他们的存在率分别为27.3%和13.6%。本研究扩展了中国汉族人群PK突变谱，为PK的遗传基础提供了进一步的证据。我们首次发现了同时与掌状角化病和植物传播发育有关的MVD，并证实了基因型-表型相关性。
BackgroundPorokeratosis (PK, MIM 175800) is a chronic autosomal dominant cutaneous keratinization disorder, which has a wide variety of clinical manifestations.ObjectivesWe analysed the molecular basis of 10 families and 12 sporadic cases with different subtypes of porokeratosis in the Chinese population.MethodsGenomic DNA was extracted from peripheral blood samples. Mutation screening was performed by direct sequencing of exons and flanking intron-exon boundaries for the entire coding region of four mevalonate pathway genes and SLC17A9 gene.ResultsWe detected three novel mutations and seven previously described mutations by direct sequence analysis of the PCR products. Mutations p.Phe249Ser and p.Asn292Ser in mevalonate decarboxylase (MVD) were the most common mutations in this PK cohort; their presence was 27.3% and 13.6% respectively.ConclusionsThis study extended the mutation spectrum of PK in the Chinese Han population and provided further evidence for the genetic basis of PK. We first identified MVD simultaneously responsible for porokeratosis palmaris et plantaris disseminate development and confirmed the genotype-phenotype correlations.