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DOI: 10.1055/s-0040-1718724
Duchenne Muscular Dystrophy and Early Onset Hypertrophic Cardiomyopathy associated with Mutations in Dystrophin and Hypertrophic Cardiomyopathy-Associated Genes
Funding This study was supported by The Israeli Ministry of Science, Technology and Space (to R.P.) and Ben-Gurion University of the Negev, Faculty of Health Sciences (to A.L.).
Abstract
Duchenne muscular dystrophy (DMD) is a progressive muscular damage disorder caused by mutations in dystrophin gene. Cardiomyopathy may first be evident after 10 years of age and increases in incidence with age. We present a boy diagnosed at 18 months with a rare phenotype of DMD in association with early-onset hypertrophic cardiomyopathy (HCM). The cause of DMD is a deletion of exons 51–54 of dystrophin gene. The cause of HCM was verified by whole exome sequencing. Novel missense variations in two genes: MAP2K5 inherited from the mother and ACTN2 inherited from the father, or de novo. The combination of MAP2K5, ACTN2, and dystrophin mutations, could be causing the HCM in our patient. This is the second patient diagnosed, at relatively young age, with DMD and HCM, with novel variations in genes known to cause HCM. This study demonstrates the need for genetic diagnosis to elucidate the underlying pathology of HCM.
* These authors contributed equally to this work.
Publikationsverlauf
Eingereicht: 24. Juni 2020
Angenommen: 12. September 2020
Artikel online veröffentlicht:
19. November 2020
© 2020. Thieme. All rights reserved.
Georg Thieme Verlag KG
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References
- 1 Bushby K, Finkel R, Birnkrant DJ. et al. DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol 2010; 9 (01) 77-93
- 2 Ryder S, Leadley RM, Armstrong N. et al. The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review. Orphanet J Rare Dis 2017; 12 (01) 79
- 3 Nigro G, Comi LI, Politano L, Bain RJ. The incidence and evolution of cardiomyopathy in Duchenne muscular dystrophy. Int J Cardiol 1990; 26 (03) 271-277
- 4 Maron BJ, Maron MS. Hypertrophic cardiomyopathy. Lancet 2013; 381 (9862): 242-255
- 5 Cirino AL, Seidman CE, Ho CY. Genetic testing and counseling for hypertrophic cardiomyopathy. Cardiol Clin 2019; 37 (01) 35-43
- 6 Sulem P, Helgason H, Oddson A. et al. Identification of a large set of rare complete human knockouts. Nat Genet 2015; 47 (05) 448-452
- 7 Chiu C, Bagnall RD, Ingles J. et al. Mutations in alpha-actinin-2 cause hypertrophic cardiomyopathy: a genome-wide analysis. J Am Coll Cardiol 2010; 55 (11) 1127-1135
- 8 Theis JL, Bos JM, Bartleson VB. et al. Echocardiographic-determined septal morphology in Z-disc hypertrophic cardiomyopathy. Biochem Biophys Res Commun 2006; 351 (04) 896-902
- 9 Nicol RL, Frey N, Pearson G, Cobb M, Richardson J, Olson EN. Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy. EMBO J 2001; 20 (11) 2757-2767
- 10 Kostareva A, Sejersen T, Sjoberg G. Genetic spectrum of cardiomyopathies with neuromuscular phenotype. Front Biosci (Schol Ed) 2013; 5: 325-340
- 11 Tandon A, Taylor MD, Cripe LH. Co-occurring Duchenne muscular dystrophy and hypertrophic cardiomyopathy in an adult with atypical cardiac phenotype. Cardiol Young 2015; 25 (02) 355-357
- 12 Beggs AH, Neumann PE, Arahata K. et al. Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy. Proc Natl Acad Sci USA 1992; 89 (02) 623-627
- 13 Todorova A, Constantinova D, Kremensky I. Dilated cardiomyopathy and new 16 bp deletion in exon 44 of the dystrophin gene: the possible role of repeated motifs in mutation generation. Am J Med Genet A 2003; 120A (01) 5-7
- 14 Nigro G, Politano L, Nigro V, Petretta VR, Comi LI. Mutation of dystrophin gene and cardiomyopathy. Neuromuscul Disord 1994; 4 (04) 371-379
- 15 Gold R, Kress W, Meurers B, Meng G, Reichmann H, Müller CR. Becker muscular dystrophy: detection of unusual disease courses by combined approach to dystrophin analysis. Muscle Nerve 1992; 15 (02) 214-218
- 16 Beggs AH, Hoffman EP, Snyder JR. et al. Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies. Am J Hum Genet 1991; 49 (01) 54-67
- 17 Muntoni F, Cau M, Ganau A. et al. Brief report: deletion of the dystrophin muscle-promoter region associated with X-linked dilated cardiomyopathy. N Engl J Med 1993; 329 (13) 921-925
- 18 Ribeiro Jr EdeA, Pinotsis N, Ghisleni A. et al. The structure and regulation of human muscle α-actinin. Cell 2014; 159 (06) 1447-1460
- 19 Hance JE, Fu SY, Watkins SC, Beggs AH, Michalak M. Alpha-actinin-2 is a new component of the dystrophin-glycoprotein complex. Arch Biochem Biophys 1999; 365 (02) 216-222
- 20 Gifford CA, Ranade SS, Samarakoon R. et al. Oligogenic inheritance of a human heart disease involving a genetic modifier. Science 2019; 364 (6443): 865-870
- 21 Kircher M, Witten DM, Jain P, O’Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet 2014; 46 (03) 310-315