Whole exome sequencing in a patient with uniparental disomy of chromosome 2 and a complex phenotype.
Whole exome sequencing in a patient with uniparental disomy of chromosome 2 and a complex phenotype.
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DOI：
10.1111/cge.12064
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发表时间：
2013-09
影响因子：
3.5
通讯作者：
Dauber A
中科院分区：
文献类型：
--
作者：
Carmichael H;Shen Y;Nguyen TT;Hirschhorn JN;Dauber A
整个外显子组测序和染色体微阵列是两项强大的技术，它们改变了研究人员寻找人类疾病潜在因果变异的能力。这项研究结合了这些工具来寻找一名患者的因果变异，该患者被发现患有2号染色体的母系单亲等体。该患者具有复杂的表型，包括骨骼和肾脏发育不良、免疫缺陷、生长障碍、视网膜退化和卵巢功能不全。在第2号染色体上发现了18个非同义、罕见的纯合子突变。此外，在其他染色体上还发现了5个具有复合杂合子突变的基因，这些基因可能导致一种与本例中发现的单亲二体无关的疾病表型。描述了几个与表型有潜在联系的候选基因，但没有一个被明确证明是因果关系。这项研究强调了使用整个外显子组测序来检测大量候选基因的潜力，这使得研究和临床环境中的解释都变得复杂。必须建立论坛，以发表和分享详细的表型和遗传型报告，以促进进一步的生物学发现和临床咨询。
Whole exome sequencing and chromosomal microarrays are two powerful technologies that have transformed the ability of researchers to search for potentially causal variants in human disease. This study combines these tools to search for causal variants in a patient found to have maternal uniparental isodisomy of chromosome 2. This subject has a complex phenotype including skeletal and renal dysplasia, immune deficiencies, growth failure, retinal degeneration, and ovarian insufficiency. Eighteen nonsynonymous, rare homozygous variants were identified on chromosome 2. Additionally, 5 genes with compound heterozygous mutations were detected on other chromosomes that could lead to a disease phenotype independent of the uniparental disomy found in this case. Several candidate genes with potential connection to the phenotype are described but none are definitively proven to be causal. This study highlights the potential for detection of a large number of candidate genes using whole exome sequencing complicating interpretation in both the research and clinical settings. Forums must be created for publication and sharing of detailed phenotypic and genotypic reports to facilitate further biological discoveries and clinical counseling.
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影响因子：
5.2
作者：
Forsythe, Elizabeth;Beales, Philip L.
通讯作者：
Beales, Philip L.
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4.8
作者：
ANCIAN, P;LAMBEAU, G;LAZDUNSKI, M
通讯作者：
LAZDUNSKI, M
影响因子：
5.2
作者：
Petit, FM;Gajdos, V;Labrune, P
通讯作者：
Labrune, P
影响因子：
4.4
作者：
Granata, F;Petraroli, A;Triggiani, M
通讯作者：
Triggiani, M