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A new discovered gene mutation in a child with dilated cardiomyopathy

Part of: Atrial Septal Defect (ASD) Ventricular Septal Defect (VSD)

Published online by Cambridge University Press:  05 April 2021

Xiaolong Chen Open the ORCID record for Xiaolong Chen [Opens in a new window] ,
Yewei Xie ,
Xiaobing Li ,
Jin Gong ,
Li Shen  and
Rufang Zhang
Xiaolong Chen
Affiliation:
Department of Cardiothoracic Surgery, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Putuo District, Shanghai, China
Yewei Xie
Affiliation:
Department of Cardiothoracic Surgery, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Putuo District, Shanghai, China
Xiaobing Li
Affiliation:
Department of Cardiothoracic Surgery, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Putuo District, Shanghai, China
Jin Gong
Affiliation:
Department of Cardiothoracic Surgery, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Putuo District, Shanghai, China
Li Shen*
Affiliation:
Department of Cardiothoracic Surgery, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Putuo District, Shanghai, China
Rufang Zhang*
Affiliation:
Department of Cardiothoracic Surgery, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Putuo District, Shanghai, China
*
Author for correspondence: Dr L. Shen and Dr R. Zhang, Department of Cardiothoracic Surgery, Shanghai Children’s Hospital, Shanghai Jiao Tong University, No.355 Luding Road, Putuo District, Shanghai 200062, China. E-mails: drshenli2018@163.com and zhangrf@shchildren.com.cn
Author for correspondence: Dr L. Shen and Dr R. Zhang, Department of Cardiothoracic Surgery, Shanghai Children’s Hospital, Shanghai Jiao Tong University, No.355 Luding Road, Putuo District, Shanghai 200062, China. E-mails: drshenli2018@163.com and zhangrf@shchildren.com.cn
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Abstract

Dilated cardiomyopathy is characterised by dilatation and impaired contraction of the left ventricle or both ventricles, which is the most common childhood cardiomyopathy. In recent years, it has been recognised that many sorts of genetic mutations may contribute to dilated cardiomyopathy. We now report a rare association of dilated cardiomyopathy with site mutation of BMPR2 gene. We did not find such an association reported in the medical literature.

Keywords

Dilated cardiomyopathychildBMPR2gene mutation

Information

Type
Brief Report
Information
Cardiology in the Young , Volume 31 , Issue 9 , September 2021 , pp. 1530 - 1531
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Copyright
© The Author(s), 2021. Published by Cambridge University Press

Characterised by dilatation and impaired contraction of the left ventricle or both ventricles, dilated cardiomyopathy is caused by various factors, which may be idiopathic, familial/genetic, viral and/or immune, alcoholic/toxic.Reference Richardson, McKenna and Bristow1 For progressive heart failure, arrhythmia, systemic embolism as the main clinical manifestations, patients have high rates of death and sudden death. At present, for lack of specific treatment at present, dilated cardiomyopathy is mainly treated with symptomatic and supportive therapy. As more and more cases with dilated cardiomyopathy are found to be associated with certain genetic mutation, gene therapy may possibly be the development direction in the future.

Case report

A male patient aged 8 years and 9 months was treated at our hospital for a progressive decline in the amount of activity. The patient presented with clear consciousness, average mental status, steady breathing, and no cyanosis of lips. Physical examination revealed precardiac prominence with a tremor, normal breathing sound in both lungs, without obvious dry or wet rales, high heart rate, normal heart rhythm, low heart sound, and a 3/6 grade continuous murmur in the apical region of the heart and between 4 and 5 ribs on the left edge of the sternum.

After stabilisation in the emergency room, the child was taken to the cardiac intensive care unit. Echocardiographic showed left ventricular globoid dilation especially, left ventricular systolic dysfunction (ejection fraction = 27.8%), severe mitral regurgitation (none mitral leaflet malformation), and moderate tricuspid regurgitation (see Fig 1).

Figure 1.

Left ventricular globoid dilation and mitral regurgitation, the width of regurgitant flow is 0.65 cm.

Corresponding supportive treatments were provided, such as use of dopamine as a cardiac stimulant, injection of frusemide for its diuretic property, and infusion of anti-shock agents. The patient suffered from frequent cardiac arrhythmia, in a form of borderline tachycardia, complete left bundle branch block or ventricular tachycardia, with a heart rate of about 160–180/minute, lasting about 1–5 minutes each time. During the examination of inherited metabolism, there were no abnormal signs seen in terms of glucose, lipid or amino acid metabolise. However, the gene test manifested a heterozygous mutation of BMPR2 gene (c.2795C > A) (See Table 1). According to clinical manifestation and auxiliary examination, the patient was diagnosed as dilated cardiomyopathy.

Table 1.

Gene test result.

AD: Autosomal dominance

Past surgery history

On account of ventricular septal defect, atrial septal defect and severe pulmonary arterial hypertension, when the patient was 2 months old, both repair of ventricular septal defect and repair of atrial septal defect were performed. The infant’s heart was functioning ordinarily at the time, although with mild tricuspid regurgitation, the mitral valve was in good condition with no occurrence of regurgitation. The outpatient follow-up lasted for 1 year after the surgery, showing no abnormality. And then subsequent visits were missed.

Discussion

Gene mutation is highly related to the pathogenesis, clinical phenotype and prognosis of dilated cardiomyopathy. An increasing number of gene mutations, including sarcomere-related genes, cytoskeleton-related genes, nuclear membrane protein-related genes, ion channel related-genes and other dilated cardiomyopathy-related genes has been found to be high associated with dilated cardiomyopathy. According to the current literature, dilated cardiomyopathy is associated with 110 nuclear protein coding genes and 24 mitochondrial DNA coding genes.Reference Kayvanpour, Sedaghat-Hamedani and Amr2–Reference Harakalova, Kummeling and Sammani5 However, BMPR2 gene mutation has not been reported to be associated with dilated cardiomyopathy.

BMPR2 gene is located on chromosome 2q31-33,Reference Nichols, Koller and Slovis6 it encodes bone morphogenetic protein type II receptor, which mainly regulates cell proliferation, differentiation and apoptosis. In pulmonary vascular circulation, BMPR2 related signalling pathway may inhibit the proliferation of small pulmonary artery vascular cells.Reference Morrell, Adnot and Archer7 About 55–70% of familial pulmonary arterial hypertension and 11–40% of idiopathic pulmonary hypertension are associated with BMPR2 gene mutation,Reference Cogan, Pauciulo and Batchman8 and the inheritance mode is autosomal dominant inheritance.

A heterozygous mutation of BMPR2 gene (c.2795c > A, p.pro932his) was found in this patient. The above mutation was missense mutation. Referring to the database of gnomAD and PubMed, the above mutation has not been reported in the past. However, in order to determine whether these mutations can lead to dilated cardiomyopathy, it is necessary to further study the BMPR2 gene mutation on animal model.

Acknowledgements

None.

Financial support

None.

Conflict of interest

None.

Ethical standards

This article does not contain any studies with human participants or animals performed by any of the authors.

References

Richardson, P, McKenna, W, Bristow, M, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology task force on the definition and classification of cardiomyopathies. Circulation 1996; 93: 841–842.Google ScholarPubMed
Kayvanpour, E, Sedaghat-Hamedani, F, Amr, A. Genotype-phenotype associations in dilated cardiomyopathy: meta-analysis on more than 8000 individuals. Clin Res Cardiol 2017; 106: 127–139.CrossRefGoogle ScholarPubMed
de Gonzalo-Calvo, D, Quezada, M, Campuzano, O, et al. Familial dilated cardiomyopathy: a multidisciplinary entity, from basic screening to novel circulating biomarkers. Int J Cardiol 2017; 228: 870–880.CrossRefGoogle ScholarPubMed
Petretta, M, Pirozzi, F, Sasso, L, et al. Review and meta analysis of the frequencyof familial dilated cardiomyopathy. Am J Cardiol 2011; 108: 1171–1176.CrossRefGoogle Scholar
Harakalova, M, Kummeling, G, Sammani, A, et al. A systematic analysis of genetic dilated cardiomyopathy reveals numerous ubiquitously expressed and muscle-specific genes. Eur J Heart Fail 2015; 17: 484–493.CrossRefGoogle ScholarPubMed
Nichols, WC, Koller, DL, Slovis, B, et al. Localization of the gene for familial primary pulmonary hypertension to chromosome 2q31–32. Nat Genet 1997; 15: 277–280.CrossRefGoogle ScholarPubMed
Morrell, NW, Adnot, S, Archer, SL, et al. Cellular and molecular basis of pulmonary arterial hypertension. J Am Coll Cardiol 2009; 54: S20–S31.CrossRefGoogle ScholarPubMed
Cogan, JD, Pauciulo, MW, Batchman, AP, et al. High frequency of BMPR2 exonic deletions/duplications in familial pulmonary arterial hypertension. Am J Resp Crit Care 2006; 174: 590–598.CrossRefGoogle ScholarPubMed
Figure 0

Figure 1. Left ventricular globoid dilation and mitral regurgitation, the width of regurgitant flow is 0.65 cm.

Figure 1

Table 1. Gene test result.