Investigation of new candidate genes in retinoblastoma using the TruSight One "clinical exome" gene panel.
Adult
Child
Child, Preschool
DNA Glycosylases
/ genetics
Exome
/ genetics
Female
Gene Expression Regulation, Neoplastic
Genetic Predisposition to Disease
/ genetics
Glucuronosyltransferase
/ genetics
Heterozygote
High-Throughput Nucleotide Sequencing
Humans
Male
Mutation, Missense
NAD(P)H Dehydrogenase (Quinone)
/ genetics
Pedigree
Promoter Regions, Genetic
Protein Interaction Maps
Receptor, Fibroblast Growth Factor, Type 4
/ genetics
Retina
Retinal Neoplasms
/ genetics
Retinoblastoma
/ genetics
Retinoblastoma Binding Proteins
/ genetics
Tretinoin
/ metabolism
Ubiquitin-Protein Ligases
/ genetics
RB1 gene
mutation
next-generation sequencing
retinoblastoma
retinoic acid pathway
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
21
02
2019
revised:
07
05
2019
accepted:
17
05
2019
pubmed:
18
6
2019
medline:
23
6
2020
entrez:
18
6
2019
Statut:
ppublish
Résumé
Retinoblastoma (Rb) is the most prevalent intraocular pediatric malignancy of the retina. Significant genetic factors are known to have a role in the development of Rb. Here, we report the mutation status of 4813 clinically significant genes in six patients with noncarrier of RB1 gene mutation and having normal RB1 promoter methylation from three families having higher risk for developing Rb in the study. A total of 27 variants were detected in the study. Heterozygous missense variants c.1162G > A (p.Gly388Arg) in the FGFR4 gene; c.559C > T (p.Pro187Ser) in the NQO1 gene were identified. The family based evaluation of the variants showed that the variant, c.714T > G (p.Tyr238Ter), in the CLEC7A gene in first family; the variant, c.55C > T (p.Arg19Ter), in the APOC3 gene and the variant, c.1171C > T (p.Gln391Ter), in the MUTYH gene in second family; and the variant, c.211G > A (p.Gly71Arg), in the UGT1A1 gene in the third family, were found statistically significant (p < 0.05). This study might be an important report on emphazing the mutational status of other genes in patients without RB1 gene mutations and having high risk for developing Rb. The study also indicates the interaction between the retinoic acid pathway and Rb oncogenesis for the first time.
Sections du résumé
BACKGROUND
Retinoblastoma (Rb) is the most prevalent intraocular pediatric malignancy of the retina. Significant genetic factors are known to have a role in the development of Rb.
METHODS
Here, we report the mutation status of 4813 clinically significant genes in six patients with noncarrier of RB1 gene mutation and having normal RB1 promoter methylation from three families having higher risk for developing Rb in the study.
RESULTS
A total of 27 variants were detected in the study. Heterozygous missense variants c.1162G > A (p.Gly388Arg) in the FGFR4 gene; c.559C > T (p.Pro187Ser) in the NQO1 gene were identified. The family based evaluation of the variants showed that the variant, c.714T > G (p.Tyr238Ter), in the CLEC7A gene in first family; the variant, c.55C > T (p.Arg19Ter), in the APOC3 gene and the variant, c.1171C > T (p.Gln391Ter), in the MUTYH gene in second family; and the variant, c.211G > A (p.Gly71Arg), in the UGT1A1 gene in the third family, were found statistically significant (p < 0.05).
CONCLUSION
This study might be an important report on emphazing the mutational status of other genes in patients without RB1 gene mutations and having high risk for developing Rb. The study also indicates the interaction between the retinoic acid pathway and Rb oncogenesis for the first time.
Identifiants
pubmed: 31207142
doi: 10.1002/mgg3.785
pmc: PMC6687622
doi:
Substances chimiques
RB1 protein, human
0
Retinoblastoma Binding Proteins
0
Tretinoin
5688UTC01R
NAD(P)H Dehydrogenase (Quinone)
EC 1.6.5.2
NQO1 protein, human
EC 1.6.5.2
Ubiquitin-Protein Ligases
EC 2.3.2.27
UGT1A1 enzyme
EC 2.4.1.-
Glucuronosyltransferase
EC 2.4.1.17
FGFR4 protein, human
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 4
EC 2.7.10.1
DNA Glycosylases
EC 3.2.2.-
mutY adenine glycosylase
EC 3.2.2.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e785Informations de copyright
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
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