A Novel Homozygous Intronic Variant in TNNT2 Associates With Feline Cardiomyopathy.
A Novel Homozygous Intronic Variant in TNNT2 Associates With Feline Cardiomyopathy.
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DOI：
10.3389/fphys.2020.608473
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发表时间：
2020
影响因子：
4
通讯作者：
Sadayappan S
中科院分区：
文献类型：
--
作者：
McNamara JW;Schuckman M;Becker RC;Sadayappan S
肥厚型心肌病（HCM）是一种遗传性心脏病，是年轻人心脏性猝死的最常见原因。由于编码肌节蛋白的基因中的大量突变，HCM被认为是肌节疾病。谜团在于发现这些突变如何导致疾病。因此，预防和/或治疗HCM的治疗仅限于侵入性手术切除或消融。心肌肌球蛋白结合蛋白-C的A31 P变体，由MYBPC 3编码，被发现在患有HCM的缅因州库恩猫队列中更为普遍。然而，MYBPC 3和MYH 7的其他突变也与其他品种猫的HCM相关。在这项研究中，我们扩大了与猫HCM相关的基因谱。使用从患有心肌病的缅因州浣熊的外周血分离的DNA进行下一代全基因组测序，该浣熊对MYBPC 3 A31 P变体测试为阴性。通过变体的风险分层，我们发现了心肌肌钙蛋白T（TNNT 2）中一种新型的纯合内含子变体。对该变体的计算机分析表明，它可能影响TNNT 2外显子3的正常剪接。父母双方都检测到突变的杂合子，但不受疾病的影响。超声心动图分析显示，先证者表现出早发性充血性心力衰竭，这是管理与治疗方案，包括ACE和醛固酮抑制剂。总之，我们是第一个证明TNNT 2突变和猫HCM之间的关联，这表明在对猫HCM进行基因检测时，该基因应包括在基因检测组中。
Hypertrophic cardiomyopathy (HCM) is a genetic disease of the heart and the most common cause of sudden cardiac death in the young. HCM is considered a disease of the sarcomere owing to the large number of mutations in genes encoding sarcomeric proteins. The riddle lies in discovering how these mutations lead to disease. As a result, treatments to prevent and/or treat HCM are limited to invasive surgical myectomies or ablations. The A31P variant of cardiac myosin binding protein-C, encoded by MYBPC3, was found to be more prevalent in a cohort of Maine Coon cats with HCM. However, other mutations in MYBPC3 and MYH7 have also been associated with HCM in cats of other breeds. In this study, we expand the spectrum of genes associated with HCM in cats. Next Generation Whole Genome sequencing was performed using DNA isolated from peripheral blood of a Maine Coon with cardiomyopathy that tested negative for the MYBPC3 A31P variant. Through risk stratification of variants, we identified a novel, homozygous intronic variant in cardiac troponin T (TNNT2). In silico analysis of the variant suggested that it may affect normal splicing of exon 3 of TNNT2. Both parents tested heterozygous for the mutation, but were unaffected by the disease. Echocardiography analyses revealed that the proband had shown early onset congestive heart failure, which is managed with a treatment regime including ACE and aldosterone inhibitors. In summary, we are the first to demonstrate the association between TNNT2 mutations and HCM in felines, suggesting that this gene should be included in the testing panel of genes when performing genetic testing for HCM in cats.
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影响因子：
3.7
作者：
Ahmad F;Banerjee SK;Lage ML;Huang XN;Smith SH;Saba S;Rager J;Conner DA;Janczewski AM;Tobita K;Tinney JP;Moskowitz IP;Perez-Atayde AR;Keller BB;Mathier MA;Shroff SG;Seidman CE;Seidman JG
通讯作者：
Seidman JG
影响因子：
4.8
作者：
Gomes, AV;Liang, JS;Potter, JD
通讯作者：
Potter, JD
影响因子：
3.5
作者：
Wang, M;Marín, A
通讯作者：
Marín, A
DOI：
10.2460/javma.2005.226.734
发表时间：
2005-03-01
影响因子：
1.9
作者：
Drourr, L;Lefbom, BK;Tyrrell, WD
通讯作者：
Tyrrell, WD
影响因子：
0.9
作者：
Ho, Carolyn Y.
通讯作者：
Ho, Carolyn Y.