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Biallelic variants in PPP1R13L cause paediatric dilated cardiomyopathy.

Publication ,  Journal Article
Robinson, HK; Zaklyazminskaya, E; Povolotskaya, I; Surikova, Y; Mallin, L; Armstrong, C; Mabin, D; Benke, PJ; Chrisant, MR; McDonald, M ...
Published in: Clin Genet
October 2020

Childhood dilated cardiomyopathy (DCM) is a leading cause of heart failure requiring cardiac transplantation and approximately 5% of cases result in sudden death. Knowledge of the underlying genetic cause can aid prognostication and clinical management and enables accurate recurrence risk counselling for the family. Here we used genomic sequencing to identify the causative genetic variant(s) in families with children affected by severe DCM. In an international collaborative effort facilitated by GeneMatcher, biallelic variants in PPP1R13L were identified in seven children with severe DCM from five unrelated families following exome or genome sequencing and inheritance-based variant filtering. PPP1R13L encodes inhibitor of apoptosis-stimulating protein of p53 protein (iASPP). In addition to roles in apoptosis, iASPP acts as a regulator of desmosomes and has been implicated in inflammatory pathways. DCM presented early (mean: 2 years 10 months; range: 3 months-9 years) and was progressive, resulting in death (n = 3) or transplant (n = 3), with one child currently awaiting transplant. Genomic sequencing technologies are valuable for the identification of novel and emerging candidate genes. Biallelic variants in PPP1R13L were previously reported in a single consanguineous family with paediatric DCM. The identification here of a further five families now provides sufficient evidence to support a robust gene-disease association between PPP1R13L and severe paediatric DCM. The PPP1R13L gene should be included in panel-based genetic testing for paediatric DCM.

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Published In

Clin Genet

DOI

EISSN

1399-0004

Publication Date

October 2020

Volume

98

Issue

4

Start / End Page

331 / 340

Location

Denmark

Related Subject Headings

  • Repressor Proteins
  • Pedigree
  • Pediatrics
  • Male
  • Intracellular Signaling Peptides and Proteins
  • Infant
  • Humans
  • Genetics & Heredity
  • Genetic Testing
  • Genetic Predisposition to Disease
 

Citation

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Robinson, H. K., Zaklyazminskaya, E., Povolotskaya, I., Surikova, Y., Mallin, L., Armstrong, C., … Ellard, S. (2020). Biallelic variants in PPP1R13L cause paediatric dilated cardiomyopathy. Clin Genet, 98(4), 331–340. https://doi.org/10.1111/cge.13812
Robinson, H. K., E. Zaklyazminskaya, I. Povolotskaya, Y. Surikova, L. Mallin, C. Armstrong, D. Mabin, et al. “Biallelic variants in PPP1R13L cause paediatric dilated cardiomyopathy.Clin Genet 98, no. 4 (October 2020): 331–40. https://doi.org/10.1111/cge.13812.
Robinson HK, Zaklyazminskaya E, Povolotskaya I, Surikova Y, Mallin L, Armstrong C, et al. Biallelic variants in PPP1R13L cause paediatric dilated cardiomyopathy. Clin Genet. 2020 Oct;98(4):331–40.
Robinson, H. K., et al. “Biallelic variants in PPP1R13L cause paediatric dilated cardiomyopathy.Clin Genet, vol. 98, no. 4, Oct. 2020, pp. 331–40. Pubmed, doi:10.1111/cge.13812.
Robinson HK, Zaklyazminskaya E, Povolotskaya I, Surikova Y, Mallin L, Armstrong C, Mabin D, Benke PJ, Chrisant MR, McDonald M, Marboe CC, Agre KE, Deyle DR, McWalter K, Douglas G, Balashova MS, Kaimonov V, Shirokova N, Pomerantseva E, Turner CL, Ellard S. Biallelic variants in PPP1R13L cause paediatric dilated cardiomyopathy. Clin Genet. 2020 Oct;98(4):331–340.
Journal cover image

Published In

Clin Genet

DOI

EISSN

1399-0004

Publication Date

October 2020

Volume

98

Issue

4

Start / End Page

331 / 340

Location

Denmark

Related Subject Headings

  • Repressor Proteins
  • Pedigree
  • Pediatrics
  • Male
  • Intracellular Signaling Peptides and Proteins
  • Infant
  • Humans
  • Genetics & Heredity
  • Genetic Testing
  • Genetic Predisposition to Disease