Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families.
Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families.
复制标题
整个外显子组测序揭示了多重血统巴基斯坦家族中已知白癜风基因变体的聚类。
DOI：
10.3390/genes14051118
复制
发表时间：
2023-05-22
期刊：
影响因子：
3.5
通讯作者：
Ahmed ZM
中科院分区：
文献类型：
--
作者：
Ishaq R;Ilyas M;Habiba U;Amin MNU;Saeed S;Raja GK;Shaiq PA;Ahmed ZM
白癜风是一种自身免疫性复杂色素沉着疾病，其特征在于皮肤表面的非色素斑，影响全球约0.5-2%的人口。确切的病因仍然是未知的，但是，白癜风被假设为一个多因素和遗传异质性条件。因此，目前的研究旨在调查白癜风的人体测量学表现和遗传谱在15个巴基斯坦血缘家庭。参与个体的临床评价显示了不同程度的疾病严重程度，平均发病年龄为23岁。大多数受影响的个体患有非节段性白癜风（NSV）。全外显子组测序分析揭示了已知白癜风相关基因的罕见变异的聚类。例如，在VF-12家族的受影响个体中，我们鉴定了PTPN 22（c.1108C>A）、NRROS（c.197C>T）和HERC 2（c.10969G>A）基因的三种新的罕见变体。所有这三种变体都取代了编码蛋白质中进化上保守的氨基酸残基，预计这些氨基酸残基会影响二级结构中的离子相互作用。尽管各种计算机算法预测这些变异个体的效应值较低，但它们在受影响个体中的聚集增加了风险等位基因的多基因负担。据我们所知，这是第一个研究，突出了白癜风的复杂病因和遗传异质性在多重血缘巴基斯坦家庭。
Vitiligo is an autoimmune complex pigmentation disease characterized by non-pigmented patches on the surface of the skin that affect approximately 0.5–2% population worldwide. The exact etiology is still unknown; however, vitiligo is hypothesized to be a multifactorial and genetically heterogeneous condition. Therefore, the current study is designed to investigate the anthropometric presentation and genetic spectrum of vitiligo in fifteen consanguineous Pakistani families. The clinical evaluation of participating individuals revealed varying degrees of disease severity, with 23 years as the average age of disease onset. The majority of the affected individuals had non-segmental vitiligo (NSV). Whole exome sequencing analysis revealed clustering of rare variants of known vitiligo-associated genes. For instance, in the affected individuals of family VF-12, we identified three novel rare variants of PTPN22 (c.1108C>A), NRROS (c.197C>T) and HERC2 (c.10969G>A) genes. All three variants replaced evolutionarily conserved amino acid residues in encoded proteins, which are predicted to impact the ionic interactions in the secondary structure. Although various in silico algorithms predicted low effect sizes for these variants individually, the clustering of them in affected individuals increases the polygenic burden of risk alleles. To our knowledge, this is the first study that highlights the complex etiology of vitiligo and genetic heterogeneity in multiplex consanguineous Pakistani families.
登录
查看更多内容
影响因子：
5
作者：
Cantón, I;Akhtar, S;Kemp, EH
通讯作者：
Kemp, EH
影响因子：
3.6
作者：
Laddha, Naresh C.;Dwivedi, Mitesh;Begum, Rasheedunnisa
通讯作者：
Begum, Rasheedunnisa
影响因子：
3.6
作者：
Kundu RV;Mhlaba JM;Rangel SM;Le Poole IC
通讯作者：
Le Poole IC
影响因子：
3.9
作者：
Richard EM;Santos-Cortez RLP;Faridi R;Rehman AU;Lee K;Shahzad M;Acharya A;Khan AA;Imtiaz A;Chakchouk I;Takla C;Abbe I;Rafeeq M;Liaqat K;Chaudhry T;Bamshad MJ;Nickerson DA;University of Washington Center for Mendelian Genomics;Schrauwen I;Khan SN;Morell RJ;Zafar S;Ansar M;Ahmed ZM;Ahmad W;Riazuddin S;Friedman TB;Leal SM;Riazuddin S
通讯作者：
Riazuddin S
影响因子：
5.9
作者：
Spritz, Richard A.
通讯作者：
Spritz, Richard A.