Nejat Mahdieh1, Maryam Hosseini Moghaddam1, Mahsa Motavaf2, Ahmad Rabbani3, Mahdieh Soveizi1, Majid Maleki3, Bahareh Rabbani1, Azin Alizadeh-Asl3. 1. Cardiogenetics Research Laboratory, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran. 2. Faculty of Biological Science, Department of Molecular Genetics, Tarbiat Modares University, Tehran, Iran. 3. Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
Abstract
BACKGROUND: MYBPC3 mutations have been described in dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). A mutation, c.3373G>A, has been reported to cause autosomal recessive form of HCM. Here, we report that this mutation can cause autosomal dominant form of DCM. METHODS: Next-generation sequencing using targeted panel of a total of 23 candidate genes and following Sanger sequencing was applied to detect causal mutations of DCM. Computational analyses were also performed using available software tools. In silico structural and functional analyses including protein modeling and prediction were done for the mutated MYBPC3 protein. RESULTS AND CONCLUSION: Targeted sequencing showed one variant c.3373G>A (p.Val1125Met) in the studied family following autosomal dominant inheritance. Computational programs predicted a high score of pathogenicity. Secondary structure of the region surrounding p.Val1125 was changed to a shortened beta-strand based on prediction of I-TASSER and Phyre2 servers with high confidence value for the mutation. cMyBP-C protein was modeled to 3dmkA. Our findings suggest that one single mutation of MYBPC3 may have different effects on the cellular mechanisms based of its zygosity. Various factors might be considered for explaining this phenomenon. This gene may have an important role in Iranian DCM and HCM patients.
BACKGROUND:MYBPC3 mutations have been described in dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). A mutation, c.3373G>A, has been reported to cause autosomal recessive form of HCM. Here, we report that this mutation can cause autosomal dominant form of DCM. METHODS: Next-generation sequencing using targeted panel of a total of 23 candidate genes and following Sanger sequencing was applied to detect causal mutations of DCM. Computational analyses were also performed using available software tools. In silico structural and functional analyses including protein modeling and prediction were done for the mutated MYBPC3 protein. RESULTS AND CONCLUSION: Targeted sequencing showed one variant c.3373G>A (p.Val1125Met) in the studied family following autosomal dominant inheritance. Computational programs predicted a high score of pathogenicity. Secondary structure of the region surrounding p.Val1125 was changed to a shortened beta-strand based on prediction of I-TASSER and Phyre2 servers with high confidence value for the mutation. cMyBP-C protein was modeled to 3dmkA. Our findings suggest that one single mutation of MYBPC3 may have different effects on the cellular mechanisms based of its zygosity. Various factors might be considered for explaining this phenomenon. This gene may have an important role in Iranian DCM and HCM patients.
Authors: Anna Posafalvi; Johanna C Herkert; Richard J Sinke; Maarten P van den Berg; Jens Mogensen; Jan D H Jongbloed; J Peter van Tintelen Journal: Eur J Hum Genet Date: 2012-12-19 Impact factor: 4.246
Authors: Heinz Jungbluth; Mathias Gautel; Martin Rees; Roksana Nikoopour; Atsushi Fukuzawa; Ay Lin Kho; Miguel A Fernandez-Garcia; Elizabeth Wraige; Istvan Bodi; Charu Deshpande; Özkan Özdemir; Hülya-Sevcan Daimagüler; Mark Pfuhl; Mark Holt; Birgit Brandmeier; Sarah Grover; Joël Fluss; Cheryl Longman; Maria Elena Farrugia; Emma Matthews; Michael Hanna; Francesco Muntoni; Anna Sarkozy; Rahul Phadke; Ros Quinlivan; Emily C Oates; Rolf Schröder; Christian Thiel; Jens Reimann; Nicol Voermans; Corrie Erasmus; Erik-Jan Kamsteeg; Chaminda Konersman; Carla Grosmann; Shane McKee; Sandya Tirupathi; Steven A Moore; Ekkehard Wilichowski; Elke Hobbiebrunken; Gabriele Dekomien; Isabelle Richard; Peter Van den Bergh; Cristina Domínguez-González; Sebahattin Cirak; Ana Ferreiro Journal: Acta Neuropathol Date: 2021-01-15 Impact factor: 17.088