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TAR syndrome: Clinical and molecular characterization of a cohort of 26 patients and description of novel noncoding variants of RBM8A
Author(s) -
Boussion Simon,
Escande Fabienne,
Jourdain AnneSophie,
Smol Thomas,
Brunelle Perrine,
Duhamel Céline,
Alembik Yves,
AttiéBitach Tania,
Baujat Geneviève,
Bazin Anne,
Bonnière Maryse,
Carassou Philippe,
Carles Dominique,
Devisme Louise,
Goizet Cyril,
Goldenberg Alice,
Grotto Sarah,
Guichet Agnès,
Jouk PierreSimon,
Loeuillet Laurence,
Mechler Charlotte,
Michot Caroline,
Pelluard Fanny,
Putoux Audrey,
Whalen Sandra,
Ghoumid Jamal,
ManouvrierHanu Sylvie,
Petit Florence
Publication year - 2020
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.24021
Subject(s) - biology , exon , genetics , rna splicing , untranslated region , gene , intron , alternative splicing , allele , messenger rna , rna
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.