TAR syndrome: Clinical and molecular characterization of a cohort of 26 patients and description of novel noncoding variants of RBM8A.
5' Untranslated Regions
Adolescent
Adult
Child
Child, Preschool
Chromosome Deletion
Chromosomes, Human, Pair 1
Cohort Studies
Congenital Bone Marrow Failure Syndromes
/ genetics
Female
Humans
Infant
Infant, Newborn
Male
Middle Aged
RNA-Binding Proteins
/ genetics
Radius
/ pathology
Thrombocytopenia
/ genetics
Upper Extremity Deformities, Congenital
/ genetics
Young Adult
RBM8A
TAR syndrome
Y14
exon junction complex
regulatory SNP
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
13
11
2019
revised:
18
02
2020
accepted:
22
03
2020
pubmed:
1
4
2020
medline:
6
11
2021
entrez:
1
4
2020
Statut:
ppublish
Résumé
Thrombocytopenia-absent radius (TAR) syndrome is characterized by radial defect and neonatal thrombocytopenia. It is caused by biallelic variants of RBM8A gene (1q21.1) with the association of a null allele and a hypomorphic noncoding variant. RBM8A encodes Y14, a core protein of the exon junction complex involved in messenger RNA maturation. To date, only two hypomorphic variants have been identified. We report on a cohort of 26 patients affected with TAR syndrome and carrying biallelic variants in RBM8A. Half patients carried a 1q21.1 deletion and one of the two known hypomorphic variants. Four novel noncoding variants of RBM8A were identified in the remaining patients. We developed experimental models enabling their functional characterization in vitro. Two variants, located respectively in the 5'-untranslated region (5'-UTR) and 3'-UTR regions, are responsible for a diminished expression whereas two intronic variants alter splicing. Our results bring new insights into the molecular knowledge of TAR syndrome and enabled us to propose genetic counseling for patients' families.
Substances chimiques
5' Untranslated Regions
0
RBM8A protein, human
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1220-1225Informations de copyright
© 2020 Wiley Periodicals, Inc.
Références
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