Whole-Exome Sequencing of Adult and Pediatric Cohorts of the Rare Vascular Disorder Systemic Capillary Leak Syndrome.
Whole-Exome Sequencing of Adult and Pediatric Cohorts of the Rare Vascular Disorder Systemic Capillary Leak Syndrome.
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DOI：
10.1097/shk.0000000000001254
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发表时间：
2019-08
期刊：
影响因子：
--
通讯作者：
Druey KM
中科院分区：
文献类型：
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作者：
Pierce R;Ji W;Chan EC;Xie Z;Long LM;Khokha M;Lakhani S;Druey KM
全身性毛细血管渗漏综合征是一种罕见的疾病，表现为低血容量性休克。遗传异常导致SCLS的程度尚不清楚。我们确定了具有特征性临床病程的儿童和成人队列。我们试图描述这两个队列的临床特征，确定可能的遗传贡献SCLS，并证明全外显子组测序（WES）可能由重症监护提供者进行。对9名成人和8名儿童SCLS患者以及可用的未受影响的一级亲属进行WES的前瞻性观察性研究。三级儿童医院和转诊研究实验室。儿童和成人SCLS。没有。患者和可用的一级亲属进行了WES。通过等位基因富集和代谢途径分析，对罕见纯合、双等位基因、新生和杂合变体的数据进行分析。SCLS儿童在年龄较小时出现类似于成人经历的发作。所有患者和亲属均接受了满意的WES。在所有SCLS患者中未发现重叠的基因变异或代谢途径。在SCLS个体受试者中鉴定出多个具有纯合或双等位基因突变的候选基因。有没有显着富集的基因与罕见的杂合变异。儿童和成人SCLS的临床特征相似。我们没有发现SCLS的一个统一的生殖系外显子遗传病因。WES在个体患者中确定了几个候选基因，以供未来研究。WES是一种可行的方法，重症监护提供者调查疾病的病因与假定的遗传贡献。
Systemic capillary leak syndrome (SCLS) is a rare disorder that presents with episodes of hypovolemic shock. The extent to which genetic abnormalities contribute to SCLS is unknown. We identified pediatric and adult cohorts with characteristic clinical courses. We sought to describe the clinical characteristics of both cohorts, identify a possible genetic contribution to SCLS, and demonstrate that whole exome sequencing (WES) may be conducted by critical care providers. Prospective observational study of WES of nine adult and eight pediatric SCLS patients and available unaffected first-degree relatives. Tertiary children’s hospitals and referral research laboratory. Children and adults with SCLS. None. Patients and available first-degree relatives underwent WES. Data were analyzed for rare homozygous, bi-allelic, de novo and heterozygous variants with allelic enrichment and metabolic pathway analyses. Children with SCLS presented at a younger age with episodes similar to those experienced by adults. All patients and available relatives underwent satisfactory WES. No overlapping gene variants or metabolic pathways were identified across all SCLS patients. Multiple candidate genes with homozygous or bi-allelic mutations were identified in individual subjects with SCLS. There was no significant enrichment of genes with rare heterozygous variants. The clinical characteristics of children and adults with SCLS are similar. We did not identify a uniform germline exomic genetic etiology for SCLS. WES identified several candidate genes in individual patients for future research. WES is a viable way for critical care providers to investigate the etiology of diseases with presumed genetic contributions.