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首页> 外文期刊>American journal of medical genetics, Part A >A biallelic truncating AEBP1 variant causes connective tissue disorder in two siblings
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A biallelic truncating AEBP1 variant causes connective tissue disorder in two siblings

机译：双挠曲截断的Aebp1变体导致两个兄弟姐妹的结缔组织障碍

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摘要

Biallelic variants in the AEBP1 gene cause a novel autosomal-recessive connective tissue disorder (CTD) reminiscent of Ehlers-Danlos Syndrome (EDS). The four previously reported individuals show considerable clinical variability. Unbiased high-throughput sequencing enables the rapid identification of additional cases for such rare entities. We identified the homozygous nonsense variant c.917dup, p.Tyr306* in AEBP1 using clinical exome sequencing in a female individual with previously unsolved CTD. Segregation testing confirmed homozygosity in the clinically affected brother and heterozygous carrier status in the healthy mother. Chromosomal microarray showed that the variant lies in a run of homozygosity, suggesting a common origin of this genomic segment. RT-PCR analysis in the mother revealed a monoallelic expression of the normal transcript supporting a nonsense-mediated mRNA decay and functional nullizygosity as disease mechanism. We describe two individuals from a fourth family with AEBP1-associated CTD. Our results further verify that autosomal-recessive inherited LOF variants in the AEBP1 gene cause clinical features of different EDS subtypes, but also of the marfanoid spectrum. As identification of further individuals is necessary to inform the clinical characterization, we stress the added value of exome sequencing for such rare diseases.
机译：AEBP1基因中的双层变体导致新型的常血剂 - 隐性结缔组织障碍（CTD）让人想起Ehlers-Danlos综合征（EDS）。这四个先前报告的个体表现出相当大的临床变异性。无偏见的高通量测序可以快速识别此类珍稀实体的额外情况。在具有以前未解决的CTD的女性个体中使用临床exome测序，我们在AEBP1中鉴定了纯合的非阵容变体C.917dup，p.Tyr306 *。分离测试确认了健康母亲临床影响的兄弟和杂合子载体地位的纯合子。染色体微阵列表明该变体在于纯合子的运行，表明该基因组片段的共同来源。母亲的RT-PCR分析显示出普通转录物的单相连表达，其支持废话介导的mRNA衰减和作为疾病机制的功能性核化学性。我们用AEBP1相关的CTD描述来自第四个家庭的两个人。我们的结果进一步验证了AEBP1基因中的常血型隐性遗传的遗传性植物体变体导致不同EDS亚型的临床特征，也导致不同EDS亚型的临床特征。由于鉴定进一步的个体是为了通知临床表征，我们应强调exome测序的增加值对这种罕见疾病。

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