Causal variants screened by whole exome sequencing in a patient with maternal uniparental isodisomy of chromosome 10 and a complicated phenotype.
Causal variants screened by whole exome sequencing in a patient with maternal uniparental isodisomy of chromosome 10 and a complicated phenotype.
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DOI：
10.3892/etm.2016.3241
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发表时间：
2016-06
影响因子：
2.7
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Li N;Ding YU;Yu T;Li J;Shen Y;Wang X;Fu Q;Shen Y;Huang X;Wang J
单亲二体性（UPD）是一种染色体对的两个拷贝均遗传自父母一方的异常情况，可能通过影响基因组印记或引起常染色体隐性变异而导致临床异常。全外显子组测序 (WES) 和染色体微阵列分析 (CMA) 是用于搜索潜在因果变异的强大技术。在本研究中，WES被用来筛选一名中国儿科患者基因组中的候选致病变异，CMA显示该患者具有母亲单亲10号染色体二倍体。这与许多严重的医疗问题有关，包括双侧耳聋、双眼失明、生长发育不良和白斑病。在 10 号染色体上总共鉴定出这些基因的 13 个罕见纯合变异。其中包括 HPS1 基因中的经典剪接变异 (c.398+5G>A)，它会导致 1 型赫曼斯基-普德拉克综合征，并可能解释患者的眼部和皮肤疾病。此外，通过表型分析发现其他染色体上的六个可能致病基因与受试者的眼部和听觉疾病相关。本研究的结果表明，WES 和 CMA 可以成功结合，以识别候选因果基因。此外，在该患者中建立了表型和基因型之间的联系。
Uniparental disomy (UPD), which is the abnormal situation in which both copies of a chromosomal pair have been inherited from one parent, may cause clinical abnormalities by affecting genomic imprinting or causing autosomal recessive variation. Whole Exome Sequencing (WES) and chromosomal microarray analysis (CMA) are powerful technologies used to search for underlying causal variants. In the present study, WES was used to screen for candidate causal variants in the genome of a Chinese pediatric patient, who had been shown by CMA to have maternal uniparental isodisomy of chromosome 10. This was associated with numerous severe medical problems, including bilateral deafness, binocular blindness, stunted growth and leukoderma. A total of 13 rare homozygous variants of these genes were identified on chromosome 10. These included a classical splice variant in the HPS1 gene (c.398+5G>A), which causes Hermansky-Pudlak syndrome type 1 and may explain the patient's ocular and dermal disorders. In addition, six likely pathogenic genes on other chromosomes were found to be associated with the subject's ocular and aural disorders by phenotypic analysis. The results of the present study demonstrated that WES and CMA may be successfully combined in order to identify candidate causal genes. Furthermore, a connection between phenotype and genotype was established in this patient.