Novel compound heterozygous CCDC40 mutations in a familial case of primary ciliary dyskinesia.
Novel compound heterozygous CCDC40 mutations in a familial case of primary ciliary dyskinesia.
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DOI：
10.3389/fped.2022.996332
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发表时间：
2022
影响因子：
2.6
通讯作者：
Wu, Yurong
中科院分区：
文献类型：
--
作者：
Zhao, Liqing;Huang, Suqiu;Wei, Wei;Zhang, Bingyao;Shi, Wenxiang;Liang, Yongzhou;Xu, Rang;Wu, Yurong
原发性纤毛运动障碍（PCD）是一种罕见的遗传性疾病，其特征是运动性纤毛功能障碍和超微结构受损。尽管进行了大量研究，但约 30% 的 PCD 病例的遗传基础仍有待阐明。在这里，我们对编码含有卷曲螺旋结构域的蛋白 40 (CCDC40) 的基因中的两个新突变进行了鉴定和功能分析，这些突变是在 PCD 家族病例中发现的。这些新的 CCDC40 突变 NM_017950.4: c.2236-2delA 和 c.2042_2046delTCACA, NP_060420.2: p.(Ile681fs) 通过全外显子组测序 (WES) 进行了鉴定。然后进行桑格测序以确认WES结果并确定先证者父母的CCDC40基因序列。 c.2042_2046delTCACA 突变破坏了蛋白质的阅读框，因此预计会产生无功能的蛋白质。使用 pcDNA3.1(+) 质粒的小基因检测，我们进一步研究了 c.2236-2delA 突变的潜在致病作用，发现该突变通过剪接破坏导致形成截短的蛋白质。因此，总之，我们鉴定了 CCDC40 基因的两个突变，可以被认为是家族性 PCD 病例中的致病性复合杂合突变，从而扩大了该疾病中 CCDC40 基因的已知突变谱。
Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by motile ciliary dysfunction and impaired ultrastructure. Despite numerous studies, the genetic basis for about 30% of PCD cases remains to be elucidated. Here, we present the identification and functional analysis of two novel mutations in the gene encoding coiled-coil domain-containing protein 40 (CCDC40), which are found in a familial case of PCD. These novel CCDC40 mutations, NM_017950.4: c.2236-2delA and c.2042_2046delTCACA, NP_060420.2: p.(Ile681fs), were identified by whole-exome sequencing (WES). Sanger sequencing was then performed to confirm the WES results and determine the CCDC40 gene sequences of the proband’s parents. The c.2042_2046delTCACA mutation disrupts the reading frame of the protein and is therefore predicted to produce a non-functional protein. Using a minigene assay with the pcDNA3.1(+) plasmid, we further investigated the potential pathogenic effects of the c.2236-2delA mutation and found that this mutation leads to formation of a truncated protein via splicing disruption. Thus, in summary, we identified two mutations of the CCDC40 gene that can be considered pathogenic compound heterozygous mutations in a case of familial PCD, thereby expanding the known mutational spectrum of the CCDC40 gene in this disease.
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DOI：
10.1007/978-1-60761-759-4_15
发表时间：
2010-01-01
期刊：
CANCER SUSCEPTIBILITY: METHODS AND PROTOCOLS
影响因子：
--
作者：
Gaildrat, Pascaline;Killian, Audrey;Tosi, Mario
通讯作者：
Tosi, Mario
影响因子：
3.7
作者：
Yang L;Banerjee S;Cao J;Bai X;Peng Z;Chen H;Huang H;Han P;Feng S;Yi N;Song X;Wu J
通讯作者：
Wu J
影响因子：
3.9
作者：
Antony, Dinu;Becker-Heck, Anita;Zariwala, Maimoona A.;Schmidts, Miriam;Onoufriadis, Alexandros;Forouhan, Mitra;Wilson, Robert;Taylor-Cox, Theresa;Dewar, Ann;Jackson, Claire;Goggin, Patricia;Loges, Niki T.;Olbrich, Heike;Jaspers, Martine;Jorissen, Mark;Leigh, Margaret W.;Wolf, Whitney E.;Daniels, M. Leigh Anne;Noone, Peadar G.;Ferkol, Thomas W.;Sagel, Scott D.;Rosenfeld, Margaret;Rutman, Andrew;Dixit, Abhijit;O'Callaghan, Christopher;Lucas, Jane S.;Hogg, Claire;Scambler, Peter J.;Emes, Richard D.;Chung, Eddie M. K.;Shoemark, Amelia;Knowles, Michael R.;Omran, Heymut;Mitchison, Hannah M.
通讯作者：
Mitchison, Hannah M.
影响因子：
4
作者：
Blanchon, Sylvain;Legendre, Marie;Amselem, Serge
通讯作者：
Amselem, Serge
影响因子：
5.6
作者：
Stevanovic N;Skakic A;Minic P;Sovtic A;Stojiljkovic M;Pavlovic S;Andjelkovic M
通讯作者：
Andjelkovic M