Radial dysplasia

Gene: RBM8A

I don't know

Comment when marking as ready: Considered green as clear causation established, however mechanism is unusual as per: Comment on mode of inheritance: Vast majority are due to a recurrent 200kb deletion on one allele (although truncations are seen) and the presence of 1 of 2 SNPs in trans. The SNPs have a MAF of 3.05% and 0.42%. Information on the SNPs previously sent to Ellen Thomas, who forwarded to Olivia Niblock regarding the LabKey list of difficult variants.

Created: 11 May 2017, 10:05 a.m.

Comment on mode of inheritance: Vast majority are due to a recurrent 200kb deletion on one allele (although truncations are seen) and the presence of 1 of 2 SNPs in trans. The SNPs have a MAF of 3.05% and 0.42%.

Created: 28 Feb 2017, 1:57 p.m.

Recognised cause of thrombocytopaenia and absent radius however requires biallelic alterations. Above PMID (22366785) shows that a mutation on one allele (in the vast majority a recurrent 200kb deletion at 1q21 but one truncation and one frameshift mutation also seen) has to be inherited in trans with a SNP in the regulatory region on the other. In view of the presence of thrombocytopaenia alone, it is unlikely to be recruited via this panel, however discussion is needed about the ability to detect this condition given the deletion / SNP combination in the majority of cases. Amber at present.

Created: 22 Feb 2017, 5:24 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Thrombocytopenia-absent radius syndrome 274000

Publications

• 22366785

RBM8A is on the panel for Radial dysplasia as an individual gene. In addition, UKGTN report a 200kb deletion for TAR syndrome, which removes 11 genes including RBM8A.

Created: 13 Oct 2016, 10:59 a.m.

Comment when marking as ready: Associated with phenotype in OMIM and G2P. At least four variants reported

Created: 29 Jul 2016, 1:53 p.m.

Green List (high evidence)

Tier 2

Created: 17 Jun 2016, 8:07 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Thrombocytopenia-absent radius syndrome 274000

Variants in this GENE are reported as part of current diagnostic practice

The UKGTN gene dossier explains that a 200kb deletion at 1q21.1 encompassing the genes; HFE2, TXNIP, PLOR3GL, ANKRD34A, LIX1L, RBM8A, GNRHR2, PEX11B, ITGA10, ANKRD35, PIAS3, NUDT1, is tested for diagnosis of Thrombocytopenia Absent-Radius Syndrome. "PLOR3GL" is likely to be POLR3GL, the correct spelling for this gene in this region.

Created: 25 Jun 2015, 10:57 a.m.