Identification of non-synonymous variations in ROBO1 and GATA5 genes in a family with bicuspid aortic valve disease.
Journal
Journal of human genetics
ISSN: 1435-232X
Titre abrégé: J Hum Genet
Pays: England
ID NLM: 9808008
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
25
02
2022
accepted:
04
04
2022
revised:
28
03
2022
pubmed:
10
5
2022
medline:
27
8
2022
entrez:
9
5
2022
Statut:
ppublish
Résumé
Bicuspid aortic valve (BAV) is the most common congenital heart defect with a high index of heritability. Patients with BAV have different clinical courses and disease progression. Herein, we report three siblings with BAV and clinical differences. Their clinical presentations include moderate to severe aortic regurgitation, aortic stenosis, and ascending aortic aneurysm. Genetic investigation was carried out using Whole-Exome Sequencing for the three patients. We identified two non-synonymous variants in ROBO1 and GATA5 genes. The ROBO1: p.(Ser327Pro) variant is shared by the three BAV-affected siblings. The GATA5: p.(Gln3Arg) variant is shared only by the two brothers who presented BAV and ascending aortic aneurysm. Their sister, affected by BAV without aneurysm, does not harbor the GATA5: p.(Gln3Arg) variant. Both variants were absent in the patients' fourth brother who is clinically healthy with tricuspid aortic valve. To our knowledge, this is the first association of ROBO1 and GATA5 variants in familial BAV with a potential genotype-phenotype correlation. Our findings are suggestive of the implication of ROBO1 gene in BAV and the GATA5: p.(Gln3Arg) variant in ascending aortic aneurysm. Our family-based study further confirms the intrafamilial incomplete penetrance of BAV and the complex pattern of inheritance of the disease.
Identifiants
pubmed: 35534675
doi: 10.1038/s10038-022-01036-x
pii: 10.1038/s10038-022-01036-x
doi:
Substances chimiques
GATA5 Transcription Factor
0
GATA5 protein, human
0
Nerve Tissue Proteins
0
Receptors, Immunologic
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
515-518Informations de copyright
© 2022. The Author(s), under exclusive licence to The Japan Society of Human Genetics.
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