Novel insights on GTPBP3-associated hypertrophic cardiomyopathy.
GTPBP3
genetic testing
hypertrophic cardiomyopathy
whole-exome sequencing
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
14
03
2023
received:
14
12
2022
accepted:
25
03
2023
medline:
8
6
2023
pubmed:
9
4
2023
entrez:
8
4
2023
Statut:
ppublish
Résumé
About 100 genes have been associated with cardiomyopathies with genotype-phenotype correlations often hard to establish. Genetic testing may help to confirm the genetic diagnosis and assess the risk of inheritance in the family. A 25-year old male with hypertrophic cardiomyopathy and fasciculoventricular accessory pathway was referred for genetic testing by his cardiologist. Targeted PRKAG2 screening and whole-exome sequencing were performed, followed by Sanger sequencing segregation analysis in the family. The PRKAG2 gene screening was negative. Whole-exome sequencing revealed the following four variants in the patient: c.181G>C (p.Ala61Pro) and c.1199C>T (p.Thr400Met) in the GTPBP3 gene, as well as c.752C>T (p.Thr251Ile) and c.1760C>T (p.Pro587Leu) in the POLG gene. Family segregation analysis showed that the patient's mother is a carrier of variant c.181G>C and the patient's paternal grandmother is a carrier of variant c.1199C>T in the GTPBP3 gene, which is in accordance with an autosomal recessive model of inheritance of the disease. Both variants in the POLG are found paternally inherited in the patient's healthy half-brother, thus are not considered disease-causing. GTPBP3 variants have been reported in patients with hypertrophic cardiomyopathy, associated with combined oxidative phosphorylation deficiency 23. These novel variants represent the probable cause of the observed clinical symptoms in the patient.
Identifiants
pubmed: 37029485
doi: 10.1002/ajmg.a.63205
doi:
Substances chimiques
GTPBP3 protein, human
EC 3.6.1.-
GTP-Binding Proteins
EC 3.6.1.-
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1804-1813Informations de copyright
© 2023 Wiley Periodicals LLC.
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