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. 2020 Jul;41(7):1220-1225.
doi: 10.1002/humu.24021. Epub 2020 Apr 6.

TAR syndrome: Clinical and molecular characterization of a cohort of 26 patients and description of novel noncoding variants of RBM8A

Simon Boussion  1   2 , Fabienne Escande  2   3 , Anne-Sophie Jourdain  2   3 , Thomas Smol  2   4 , Perrine Brunelle  2   3 , Céline Duhamel  2 , Yves Alembik  5 , Tania Attié-Bitach  6 , Geneviève Baujat  7 , Anne Bazin  8 , Maryse Bonnière  6 , Philippe Carassou  9 , Dominique Carles  10 , Louise Devisme  2   11 , Cyril Goizet  12 , Alice Goldenberg  13 , Sarah Grotto  14 , Agnès Guichet  15 , Pierre-Simon Jouk  16 , Laurence Loeuillet  17 , Charlotte Mechler  18 , Caroline Michot  7 , Fanny Pelluard  19 , Audrey Putoux  20   21 , Sandra Whalen  22 , Jamal Ghoumid  1   2 , Sylvie Manouvrier-Hanu  1   2 , Florence Petit  1   2
Affiliations

TAR syndrome: Clinical and molecular characterization of a cohort of 26 patients and description of novel noncoding variants of RBM8A

Simon Boussion et al. Hum Mutat. 2020 Jul.

Abstract

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.

Keywords: RBM8A; TAR syndrome; Y14; exon junction complex; regulatory SNP.

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References

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