更新于：2024-11-01

CCDC40

更新于：2024-11-01

基本信息

别名

CCDC40、CFAP172、CILD15

+ [6]

简介

Required for assembly of dynein regulatory complex (DRC) and inner dynein arm (IDA) complexes, which are responsible for ciliary beat regulation, thereby playing a central role in motility in cilia and flagella (PubMed:21131974). Probably acts together with CCDC39 to form a molecular ruler that determines the 96 nanometer (nm) repeat length and arrangements of components in cilia and flagella (By similarity). Not required for outer dynein arm complexes assembly. Required for axonemal recruitment of CCDC39 (PubMed:21131974).

关联

项与 CCDC40 相关的药物

ETH-42

靶点

CCDC40

作用机制

CCDC40调节剂

在研机构

ETHRIS GmbH

原研机构

ETHRIS GmbH

在研适应症

纤毛运动障碍

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 CCDC40 相关的临床结果

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100 项与 CCDC40 相关的转化医学

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0 项与 CCDC40 相关的专利（医药）

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项与 CCDC40 相关的文献（医药）

2024-11-01·Thorax

Impact of TAS2R38 polymorphisms on nasal nitric oxide and Pseudomonas infections in primary ciliary dyskinesia: relation to genotype

Article

作者: Peroni, Diego ; Pifferi, Massimo ; Bush, Andrew ; Cangiotti, Angela M ; Donzelli, Gabriele ; Guazzo, Raffaella ; Piazza, Michele ; Boner, Attilio ; Bertini, Veronica ; Caligo, Maria Adelaide ; Bertolucci, Giulia ; Maj, Debora ; Valetto, Angelo ; Doccioli, Chiara ; Michelucci, Angela

Objective Primary ciliary dyskinesia (PCD) severity has been related to genotype and levels of nasal nitric oxide (nNO). The most common TAS2R38 haplotypes (PAV/PAV, PAV/AVI, AVI/AVI) encoding the bitter taste receptor can affect nNO levels and thus could play a role in the susceptibility to respiratory infections. We assessed the impact of these polymorphisms on nNO production and Pseudomonas aeruginosa ( P.a .) infections in different PCD genotypes. Methods Prospective, longitudinal, single-centre study in patients with PCD with known genotype and one of three TAS2R38 haplotypes evaluated for up to 10 years. We related nNO values to TAS2R38 haplotypes in all patients, and in the three most frequent genotypes ( CCDC39/CCDC40 , DNAH5 , DNAH11 ). In the genetic group(s) with different mean trends of nNO in relation to the polymorphism, we evaluated longitudinal lung function as a clinical outcome measure. We also studied any associations between the prevalence of chronic P.a . infection and PAV alleles. Linear mixed-effects models were used to evaluate longitudinal associations. Results 119 patients with PCD underwent 1116 study visits. Only in the DNAH11 mutations group was there a mean trend of nNO production which was significantly higher in PAV/PAV than AVI/AVI haplotype (p=0.033), with a better trend in spirometric and plethysmographic parameters. In patients with DNAH11 mutations the PAV allele was also associated with a significantly reduced prevalence of chronic P.a . infection. Conclusion TAS2R38 may be a modifier gene for PCD severity, but only in mild phenotype disease. Further study of TAS2R38 polymorphisms might enable new management strategies to prevent chronic P.a . infections.

2024-11-01·Clinical Genetics

Genetics of 67 patients of suspected primary ciliary dyskinesia from India

Article

作者: Faruq, Mohammed ; Mathews, Susi ; Shamim, Uzma ; Jindal, Shishir ; Soni, Akshita ; Kabra, Sushil K. ; Lodha, Rakesh ; Ahuja, Vanshika ; Sharma, Pooja ; Arava, Sudheer K. ; Yadav, Subhash C. ; Jat, Kana Ram ; Uppilli, Bharathram ; Bari, Shreya

AbstractData are limited on the genetic profile of primary ciliary dyskinesia (PCD) from developing countries. Here, we report one of the first study on genetic profile of patients with suspected PCD from India. In this prospective cross‐sectional study, we enrolled 162 children with suspected PCD. We recorded clinical features, relevant laboratory tests for PCD and performed whole exome sequencing (WES). We are reporting 67 patients here who had positive variant/s on WES. We had 117 variants in 40 genes among 67 patients. Among the 108 unique variants, 33 were categorized as pathogenic or likely pathogenic (P/LP). We had nine novel variants in out cohort. The 29 definite PCD cases, diagnosed by composite reference standards, had variants in 16 genes namely LRRC6/DNAAF11 (5), DNAH5 (3), CCDC39 (3), HYDIN (3), DNAH11 (2), CCDC40 (2), CCDC65 (2) and one each DNAAF3, DNAAF2, CFAP300, RPGR, CCDC103, CCDC114, SPAG1, DNAI1, and DNAH14. To conclude, we identified 108 unique variants in 40 genes among 67 patients. The common genes involved in definite cases of PCD in Indian patients were LRRC6, DNAH5, CCDC39, and HYDIN. Our findings suggest a need to develop a separate genetic panel for PCD in the Indian population.

2024-08-01·European Respiratory Journal

Analyses of 1236 genotyped primary ciliary dyskinesia individuals identify regional clusters of distinct DNA variants and significant genotype–phenotype correlations

Article

作者: Roehmel, Jobst F ; Dworniczak, Bernd ; Kouis, Panayiotis ; Wetzke, Martin ; Yiallouros, Panayiotis ; Athanazio, Rodrigo A ; Nielsen, Kim G ; Gracci, Serena ; Pifferi, Massimo ; Raidt, Johanna ; Mall, Marcus A ; Gwozdziewicz, Karolina ; von Hardenberg, Sandra ; Loebinger, Michael R ; Hansen, Christine R ; Lorent, Natalie ; Varghese, Julian ; Boon, Mieke ; Emiralioğlu, Nagehan ; Kötz, Karsten ; Shoemark, Amelia ; Riepenhausen, Sarah ; Maj, Debora ; Fonnesu, Rossella ; Ziętkiewicz, Ewa ; Sperstad Kennelly, Synne ; Mitchison, Hannah M ; Balinotti, Juan E ; Özçelik, Ugur ; Thomas, Simon ; Haarman, Eric G ; Körner, Robert W ; Pogorzelski, Andrzej ; Walker, Woolf T ; Bode, Sebastian F N ; Aviram, Micha ; Omran, Heymut ; Sutharsan, Sivagurunathan ; Schlegtendal, Anne ; Rumman, Nisreen ; Ullmann, Nicola ; Borrelli, Melissa ; Hogg, Claire ; Dehlink, Eleonora ; Kerem, Eitan ; Nöthe-Menchen, Tabea ; Witt, Michal ; Holgersen, Mathias G ; Zschocke, Anna ; Carr, Siobhan B ; Mazurek, Henryk ; Martinu, Vendula ; Lucas, Jane S ; Amirav, Israel ; Durdik, Peter ; Bar-On, Ophir ; Rovira-Amigo, Sandra ; Große-Onnebrink, Jörg ; Pennekamp, Petra ; Marthin, June K ; Erdem, Ela ; Diepenhorst, Sandra ; Staar, Ben O ; Crowley, Suzanne ; Olbrich, Heike ; Ringshausen, Felix C

BackgroundPrimary ciliary dyskinesia (PCD) represents a group of rare hereditary disorders characterised by deficient ciliary airway clearance that can be associated with laterality defects. We aimed to describe the underlying gene defects, geographical differences in genotypes and their relationship to diagnostic findings and clinical phenotypes.MethodsGenetic variants and clinical findings (age, sex, body mass index, laterality defects, forced expiratory volume in 1 s (FEV1)) were collected from 19 countries using the European Reference Network's ERN-LUNG international PCD Registry. Genetic data were evaluated according to American College of Medical Genetics and Genomics guidelines. We assessed regional distribution of implicated genes and genetic variants as well as genotype correlations with laterality defects and FEV1.ResultsThe study included 1236 individuals carrying 908 distinct pathogenic DNA variants in 46 PCD genes. We found considerable variation in the distribution of PCD genotypes across countries due to the presence of distinct founder variants. The prevalence of PCD genotypes associated with pathognomonic ultrastructural defects (mean 72%, range 47–100%) and laterality defects (mean 42%, range 28–69%) varied widely among countries. The prevalence of laterality defects was significantly lower in PCD individuals without pathognomonic ciliary ultrastructure defects (18%). The PCD cohort had a reduced median FEV1z-score (−1.66). Median FEV1z-scores were significantly lower inCCNO(−3.26),CCDC39(−2.49) andCCDC40(−2.96) variant groups, while the FEV1z-score reductions were significantly milder inDNAH11(−0.83) andODAD1(−0.85) variant groups compared to the whole PCD cohort.ConclusionThis unprecedented multinational dataset of DNA variants and information on their distribution across countries facilitates interpretation of the genetic epidemiology of PCD and indicates that the genetic variant can predict diagnostic and phenotypic features such as the course of lung function.