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首页> 外文期刊>Journal of genetics >Evidence of digenic inheritance in autoinflammation-associated genes
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Evidence of digenic inheritance in autoinflammation-associated genes

机译：自发炎症相关基因中双基因遗传的证据

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Familial Mediterranean fever (FMF) has traditionally been considered as a monogenic autosomal recessive disorder caused by mutations in the MEFV gene with highest incidence among Mediterranean populations. In a considerable number of patients with typical FMF, only one MEFV mutation was identified and the possibility that more than one autoinflammatory gene may be responsible for their disease was investigated. In the present study, an extensive search for possiblemutations in three hereditary recurrent fever (HRF) genes was performed in 128 MEFV heterozygous Greeka€“Cypriots clinically diagnosed based on their phenotype with FMF-like disease from a previous study. Sequence analysis was performedfor MVK, TNFRSF1A and NLRP3 genes which is also known to cause HRFs. In total, three patients were identified with heterozygous mutations and a second mutation in an autoinflammatory gene. Two patients carried a MEFVmutation and a NLRP3 mutation, and an additional third carried a MEFV mutation and a TNFRSF1A mutation. Patient 1 carried MEFV p.[Val726Ala] (NM_000243.2:c.2177TC) and NLRP3 p.[Val198Met] (NM_001243133.1:c.592GA) variants and patient 2 carried MEFV p.[Glu148Gln] (NM_000243.2:c.442GC) variant which is of uncertain significance and NLRP3 p.[Arg176Trp] (NM_001243133.1:c.526CT). Lastly, patient 3 was identified to carry MEFV p.[Met694Val] (NM_000243.2:c.2080AG) and TNFRSF1A p.[Arg121Gln] (NM_001065.3:c.362GA) variants. The results from this study indicate that screening of genes known to cause HRFs in patients already identified with a single MEFV mutation, can reveal quite rare but potentially causative mutational combinations at different loci. Such interaction provide further evidence for possible locusa€“locus interactions and phenotypes resulting from digenic inheritance.
机译：传统上，家族性地中海热（FMF）被认为是由MEFV基因突变引起的单基因常染色体隐性遗传性疾病，在地中海人群中发病率最高。在相当多的典型FMF患者中，仅鉴定出一种MEFV突变，并研究了一种以上的自身炎症基因可能导致其疾病的可能性。在本研究中，对128个MEFV杂合性希腊裔希腊人进行了广泛的搜索，以寻找三个遗传性反复发热（HRF）基因的突变，这些塞浦路斯人是根据先前研究中具有FMF样疾病的表型进行临床诊断的。对已知也引起HRF的MVK，TNFRSF1A和NLRP3基因进行了序列分析。总共鉴定出三名患者具有自发性基因杂合突变和第二个突变。两名患者进行了MEFV突变和NLRP3突变，另外三例进行了MEFV突变和TNFRSF1A突变。患者1携带MEFV p。[Val726Ala]（NM_000243.2：c.2177T> C）和NLRP3 p。[Val198Met]（NM_001243133.1：c.592G> A）变体，患者2携带MEFV p。[Glu148Gln]（ NM_000243.2：c.442G> C）变体，其不确定性和NLRP3 p。[Arg176Trp]（NM_001243133.1：c.526C> T）。最后，确定患者3携带MEFV p。[Met694Val]（NM_000243.2：c.2080A> G）和TNFRSF1A p。[Arg121Gln]（NM_001065.3：c.362G> A）变体。这项研究的结果表明，在已经鉴定出具有单一MEFV突变的患者中筛选已知可引起HRF的基因，可以揭示在不同基因座上相当罕见但潜在的致病突变组合。这种相互作用为双基因遗传可能引起的基因座相互作用和表型提供了进一步的证据。

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