Bi-allelic loss of function variants of
Abnormalities, Multiple
/ diagnosis
Alleles
Computational Biology
/ methods
Gene Expression
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Hernia, Diaphragmatic
/ diagnosis
Humans
Induced Pluripotent Stem Cells
/ cytology
Loss of Function Mutation
Mutation, Missense
Scoliosis
/ congenital
Spine
/ abnormalities
T-Box Domain Proteins
/ genetics
TBX6
bi-allelic mutation
congenital scoliosis
mislocalisation
spondylocostal dysostosis
Journal
Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
04
12
2018
revised:
22
03
2019
accepted:
24
03
2019
pubmed:
25
4
2019
medline:
12
6
2020
entrez:
25
4
2019
Statut:
ppublish
Résumé
Congenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms in We recruited 200 patients with CS or SCD and investigated We identified five 16p11.2 deletions, one splice-site variant and five missense variants in 10 patients. In vitro functional assays for missense variants identified in the previous and present studies demonstrated that most of the variants caused abnormal localisation of TBX6 proteins. We confirmed mislocalisation of TBX6 proteins in presomitic mesoderm cells induced from SCD patient-derived iPS cells. In induced cells, we found decreased mRNA expressions of Our study suggests that bi-allelic loss of function variants of
Sections du résumé
BACKGROUND
Congenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms in
METHODS
We recruited 200 patients with CS or SCD and investigated
RESULTS
We identified five 16p11.2 deletions, one splice-site variant and five missense variants in 10 patients. In vitro functional assays for missense variants identified in the previous and present studies demonstrated that most of the variants caused abnormal localisation of TBX6 proteins. We confirmed mislocalisation of TBX6 proteins in presomitic mesoderm cells induced from SCD patient-derived iPS cells. In induced cells, we found decreased mRNA expressions of
CONCLUSIONS
Our study suggests that bi-allelic loss of function variants of
Identifiants
pubmed: 31015262
pii: jmedgenet-2018-105920
doi: 10.1136/jmedgenet-2018-105920
doi:
Substances chimiques
T-Box Domain Proteins
0
TBX6 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
622-628Informations de copyright
© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.