Identification of a genetic locus for ichthyosis vulgaris on chromosome 10q22.3-q24.2
Identification of a genetic locus for ichthyosis vulgaris on chromosome 10q22.3-q24.2
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DOI：
10.1038/sj.jid.5701191
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发表时间：
2008-06-01
影响因子：
6.5
通讯作者：
Wang, Qing K.
中科院分区：
文献类型：
--
作者：
Liu, Ping;Yang, Qingyu;Wang, Qing K.
寻常型鱼鳞病(IV)是最常见的遗传性疾病之一，估计中国的患病率为2.29%。到目前为止，只鉴定了一个与IV有关的基因，即微丝蛋白基因(Flg)，但存在遗传异质性。本研究对两个常染色体显性遗传性IV中国家系进行了遗传学研究。在这两个家庭中，Flg基因首次被排除为致病基因。对较大的家系进行全基因组连锁分析，以确定一个新的IV遗传位点。染色体10q22.3-q24.2上的标记被鉴定为显著连锁，最高LOD得分为3.19。没有其他标记显示LOD得分为>；1.5。精细定位在标记D10S569和D10S1709之间20.7 cM的区域内确定了新的遗传位点。第二个家系也与相同的10q22.3-q24.2区域存在正连锁。两个家系的最高LOD评分为3.95分。两个独立家系的连锁鉴定提供了强有力的遗传证据，表明IV的一个先前未报道的基因位于染色体10q22.3-q24.2上。未来对10q IV基因座候选基因的研究将确定一个特定的基因，这将为IV的发病机制提供深入的见解。
Ichthyosis vulgaris (IV) is one of the most commonly inherited disorders and has an estimated prevalence rate of 2.29% in China. To date, only one gene responsible for IV, the filaggrin gene (FLG), was identified, but genetic heterogeneity exists. In this study, two Chinese families with autosomal-dominant IV were genetically characterized. The FLG gene was first excluded as the disease-causing gene in the two families. The larger family was then characterized by genome-wide linkage analysis to identify a new genetic locus for IV. Significant linkage was identified with markers on chromosome 10q22.3-q24.2 with a maximum LOD score of 3.19. No other markers showed a LOD score of > 1.5. Fine mapping defined the new genetic locus within a 20.7 cM region between markers D10S569 and D10S1709. The second family also showed positive linkage to the same 10q22.3-q24.2 region. The combined maximum LOD score in the two families was 3.95. Identification of linkage in two independent families provides strong genetic evidence that a previously unreported gene for IV is located on chromosome 10q22.3-q24.2. Future studies of the candidate genes at the 10q IV locus will identify a specific gene, which will provide insights into the pathogenesis of IV.