#612877
Table of Contents
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1BB (CMD1BB) is caused by homozygous mutation in the desmoglein-2 gene (DSG2; 125671) on chromosome 18q12.
Dilated cardiomyopathy-1BB (CMD1BB) is a life-threatening, intractable disease characterized by ventricular dilation and thinning (Shiba et al., 2021).
For a phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200).
Shiba et al. (2021) reported a patient with a homozygous nonsense mutation in the DSG2 gene (125671.0010) who was diagnosed with a dilated heart, reduced left ventricular contraction, and high pulmonary wedge pressure at 15 years of age. Electrocardiogram at 21 years of age showed premature ventricular contractions and an intraventricular conduction disturbance. Due to uncontrollable ventricular tachycardia, he had a ventricular assist device placed at age 28. Cardiac tissue from the patient demonstrated diffuse fibrosis, cardiomyocyte size variation, intracellular vacuolated structures, and absence of desmoglein-2 staining in intercalated discs.
In a man with dilated cardiomyopathy who had severely decreased cardiac function and underwent cardiac transplantation at 44 years of age, Posch et al. (2008) identified homozygosity for a missense mutation in the DSG2 gene (V55M; 125671.0009). The proband's father, who had less severe disease with a later onset, was heterozygous for the mutation, as was his asymptomatic mother; his paternal grandfather had died of heart failure at 57 years of age. The proband had no abnormalities of skin or hair. Posch et al. (2008) subsequently screened 538 CMD patients for the DSG2 V55M variant and identified 13 unrelated carriers (2.4%); the variant was also found in 1 (0.23%) of 432 individuals without CMD (p less than 0.006). In a total of 1,228 cases and controls, the authors found significant association between the DSG2 V55M variant and CMD (p less than 0.007). Immunostaining and electron microscopy of explanted left ventricular wall myocardium from the homozygous proband revealed pale, irregularly shaped intercalated discs with an indistinct inner structure and significantly shorter desmosomes compared to wildtype.
Shiba et al. (2021) identified a homozygous nonsense mutation in the DSG2 gene (R119X; 125671.0010) in a patient with CMD1BB. Both parents were heterozygous for the mutation and asymptomatic. Cardiac tissue from the patient demonstrated diffuse fibrosis and cardiomyocyte size variation, and immunohistochemical analysis revealed absence of desmoglein-2 in intercalated discs. Immunostaining in induced pluripotent stem cells (iPSCs) derived from the patient demonstrated absence of desmoglein-2 protein.
Posch, M.G., Posch, M. J., Geier, C., Erdmann, B., Mueller, W., Richter, A., Ruppert, V., Pankuweit, S., Maisch, B., Perrot, A., Buttgereit, J., Dietz, R., Haverkamp, W., Ozcelik, C. A missense variant in desmoglein-2 predisposes to dilated cardiomyopathy. Molec. Genet. Metab. 95: 74-80, 2008. [PubMed: 18678517, related citations] [Full Text]
Shiba, M., Higo, S., Kondo, T., Li, J., Liu, L., Ikeda, Y., Kohama, Y., Kameda, S., Tabata, T., Inoue, H., Nakamura, S., Takeda, M., Ito, E., Takashima, S., Miyagawa, S., Sawa, Y., Hikoso, S., Sakata, Y. Phenotypic recapitulation and correction of desmoglein-2-deficient cardiomyopathy using human-induced pluripotent stem cell-derived cardiomyocytes. Hum. Molec. Genet. 30: 1384-1397, 2021. [PubMed: 33949662, images, related citations] [Full Text]
ORPHA: 154; DO: 0110458;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 18q12.1 | Cardiomyopathy, dilated, 1BB | 612877 | Autosomal recessive | 3 | DSG2 | 125671 |
A number sign (#) is used with this entry because of evidence that dilated cardiomyopathy-1BB (CMD1BB) is caused by homozygous mutation in the desmoglein-2 gene (DSG2; 125671) on chromosome 18q12.
Dilated cardiomyopathy-1BB (CMD1BB) is a life-threatening, intractable disease characterized by ventricular dilation and thinning (Shiba et al., 2021).
For a phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy, see CMD1A (115200).
Shiba et al. (2021) reported a patient with a homozygous nonsense mutation in the DSG2 gene (125671.0010) who was diagnosed with a dilated heart, reduced left ventricular contraction, and high pulmonary wedge pressure at 15 years of age. Electrocardiogram at 21 years of age showed premature ventricular contractions and an intraventricular conduction disturbance. Due to uncontrollable ventricular tachycardia, he had a ventricular assist device placed at age 28. Cardiac tissue from the patient demonstrated diffuse fibrosis, cardiomyocyte size variation, intracellular vacuolated structures, and absence of desmoglein-2 staining in intercalated discs.
In a man with dilated cardiomyopathy who had severely decreased cardiac function and underwent cardiac transplantation at 44 years of age, Posch et al. (2008) identified homozygosity for a missense mutation in the DSG2 gene (V55M; 125671.0009). The proband's father, who had less severe disease with a later onset, was heterozygous for the mutation, as was his asymptomatic mother; his paternal grandfather had died of heart failure at 57 years of age. The proband had no abnormalities of skin or hair. Posch et al. (2008) subsequently screened 538 CMD patients for the DSG2 V55M variant and identified 13 unrelated carriers (2.4%); the variant was also found in 1 (0.23%) of 432 individuals without CMD (p less than 0.006). In a total of 1,228 cases and controls, the authors found significant association between the DSG2 V55M variant and CMD (p less than 0.007). Immunostaining and electron microscopy of explanted left ventricular wall myocardium from the homozygous proband revealed pale, irregularly shaped intercalated discs with an indistinct inner structure and significantly shorter desmosomes compared to wildtype.
Shiba et al. (2021) identified a homozygous nonsense mutation in the DSG2 gene (R119X; 125671.0010) in a patient with CMD1BB. Both parents were heterozygous for the mutation and asymptomatic. Cardiac tissue from the patient demonstrated diffuse fibrosis and cardiomyocyte size variation, and immunohistochemical analysis revealed absence of desmoglein-2 in intercalated discs. Immunostaining in induced pluripotent stem cells (iPSCs) derived from the patient demonstrated absence of desmoglein-2 protein.
Posch, M.G., Posch, M. J., Geier, C., Erdmann, B., Mueller, W., Richter, A., Ruppert, V., Pankuweit, S., Maisch, B., Perrot, A., Buttgereit, J., Dietz, R., Haverkamp, W., Ozcelik, C. A missense variant in desmoglein-2 predisposes to dilated cardiomyopathy. Molec. Genet. Metab. 95: 74-80, 2008. [PubMed: 18678517] [Full Text: https://doi.org/10.1016/j.ymgme.2008.06.005]
Shiba, M., Higo, S., Kondo, T., Li, J., Liu, L., Ikeda, Y., Kohama, Y., Kameda, S., Tabata, T., Inoue, H., Nakamura, S., Takeda, M., Ito, E., Takashima, S., Miyagawa, S., Sawa, Y., Hikoso, S., Sakata, Y. Phenotypic recapitulation and correction of desmoglein-2-deficient cardiomyopathy using human-induced pluripotent stem cell-derived cardiomyocytes. Hum. Molec. Genet. 30: 1384-1397, 2021. [PubMed: 33949662] [Full Text: https://doi.org/10.1093/hmg/ddab127]
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