Deleterious fibronectin type III-related gene variants may induce a spinal extradural arachnoid cyst: an exome sequencing study of identical twin cases
Deleterious fibronectin type III-related gene variants may induce a spinal extradural arachnoid cyst: an exome sequencing study of identical twin cases
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有害的纤连蛋白 III 型相关基因变异可能诱发脊髓硬膜外蛛网膜囊肿：同卵双胞胎病例的外显子组测序研究
DOI：
10.1007/s00381-021-05137-4
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Morota Nobuhito
中科院分区：
文献类型：
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作者：
Hana Taijun;Ogiwara Hideki;Migita Ohsuke;Nakabayashi Kazuhiko;Hata Kenichiro;Morota Nobuhito
目的尽管进行了大量研究，但脊髓硬膜外蛛网膜囊肿（SEDAC）（一种与神经系统症状相关的病变）的病因仍不清楚。在这项基因组双胞胎研究中，我们研究了 SEDAC 的遗传病因。方法受试者是同卵双胞胎，他们在相同的椎骨水平上发育出非常相似的 SEDAC。因此，我们使用下一代测序仪对双胞胎及其父母的基因组材料进行了全外显子组测序分析。此外，我们还确定了他们的详细家族史并分析了家族谱系。结果谱系分析表明某些家族成员中可能存在 SEDAC，这表明存在遗传性疾病。使用专门构建的算法对测序数据进行分析和过滤，从而鉴定出 155 个新的单核苷酸多态性 (SNP)，其中 118 个编码错义或无义变体。对这些 SNP 等位基因编码的蛋白质的功能分析揭示了纤连蛋白 III 型 (FN3) 蛋白质结构域的强烈富集 (q= 0.00576)。具体而言，数据表明，影响纤连蛋白 1 (FN1，p.P969S) 的 FN3 蛋白结构域的错义变异可能是 SEDAC 的致病突变。结论数据表明，纤连蛋白相关基因的有害突变可能导致 SEDAC。特别是，怀疑 FN1 的变体可能是本文研究的双胞胎病例中 SEDAC 的原因。需要对大量案例进行详细研究。
PurposeDespite numerous studies, the etiology of spinal extradural arachnoid cyst (SEDAC), a lesion associated with neurological symptoms, remains unknown. In this genomic twin study, we investigated the genetic etiology of SEDACs.MethodsThe subjects were identical twins who developed notably similar SEDACs at the same vertebral level. Accordingly, we performed whole-exome sequencing analyses of genomic material from the twins and their parents using a next-generation sequencer. Additionally, we determined their detailed family history and analyzed the family pedigree.ResultsThe pedigree analysis suggested the potential presence of SEDACs in certain family members, indicating a genetic disease. Sequenced data were analyzed and filtered using a purpose-built algorithm, leading to the identification of 155 novel single-nucleotide polymorphisms (SNPs), of which 118 encoded missense or nonsense variants. A functional analysis of the proteins encoded by these SNP alleles revealed strong enrichment for the fibronectin type III (FN3) protein domain (q= 0.00576). Specifically, the data indicated that a missense variant affecting the FN3 protein domain of fibronectin 1 (FN1,p.P969S) can be the causal mutation underlying the SEDACs.ConclusionThe data suggest that deleterious mutations in fibronectin-related genes may cause SEDACs. In particular, it was suspected that a variant ofFN1may be the cause of the SEDACs in the twin cases studied herein. Detailed studies with a larger number of cases are needed.