Two rare PROX1 variants in patients with lymphedema.
Mol Genet Genomic Med
; 8(10): e1424, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32757260
ABSTRACT
BACKGROUND:
The PROX1 gene is specifically expressed in a subpopulation of endothelial cells that, by budding and sprouting, give rise to the lymphatic system. It also plays a critical role in neurogenesis and during development of many organs, such as the eye lens, liver, and pancreas.METHODS:
We used next-generation sequencing (NGS) to sequence the DNA of a cohort of 246 Italian patients with lymphatic malformations. We first investigated 29 known disease-causing genes 235 of 246 patients tested negative and were then retested for a group of candidate genes, including PROX1, selected from a database of mouse models. The aim of the study was to define these patients' genotypes and explore the role of the candidate gene PROX1 in lymphedema.RESULTS:
Two of 235 probands were found to carry rare heterozygous missense variants in PROX1. In silico analysis of these variants-p.(Leu590His) and p.(Gly106Asp)-indicates that the overall protein structure was altered by changes in interactions between nearby residues, leading to functional protein defects.CONCLUSIONS:
Our results suggest that PROX1 is a new candidate gene for predisposition to lymphedema.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Homeodomínio
/
Proteínas Supressoras de Tumor
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Linfedema
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Mol Genet Genomic Med
Ano de publicação:
2020
Tipo de documento:
Article