Biallelic variants in PPP1R13L cause paediatric dilated cardiomyopathy
| Autor: | P.J. Benke, Elena Zaklyazminskaya, L. Mallin, C. Armstrong, C.C. Marboe, Marie T. McDonald, Vladimir Kaimonov, D. Mabin, M.S. Balashova, Natalia Shirokova, H.K. Robinson, Inna S. Povolotskaya, Ganka Douglas, D.R. Deyle, Claire L. S. Turner, Kirsty McWalter, Ekaterina Pomerantseva, M.R. Chrisant, Sian Ellard, Yulia Surikova, Katherine Agre |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cardiomyopathy Dilated Male Candidate gene 030105 genetics & heredity Bioinformatics LEOPARD Syndrome Sudden death Pediatrics DNA sequencing 03 medical and health sciences Genetics medicine Humans Exome Genetic Predisposition to Disease Genetic Testing Child Genetics (clinical) Alleles Genetic testing medicine.diagnostic_test business.industry Intracellular Signaling Peptides and Proteins Infant Dilated cardiomyopathy medicine.disease Pedigree Transplantation Repressor Proteins 030104 developmental biology Child Preschool Female business |
| Zdroj: | Clinical geneticsREFERENCES. 98(4) |
| ISSN: | 1399-0004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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