Radial dysplasia

Gene: UBE2T

Comment when marking as ready: Three unrelated cases noted from reviews and some functional work. Therefore considered appropriate for inclusion. Note that the reported mutational spectrum includes multi-exonic deletions however. FA is associated with radial dysplasia in some, therefore included.

Created: 11 May 2017, 2:15 p.m.

Comment on list classification: Upgraded status from Red to Green due to literature search.

Created: 22 Feb 2017, 5:30 p.m.

Comment on publications: Evidence for 3 unrelated cases.
PMID: 26046368 Reports 2 unrelated Japanese patients with Fanconi anemia, complementation group T. A heterozygous missense mutation leading to p.Q2E was uncovered in both patients. Additionally, both patients harbored unique mutations in their second alleles, a 23-kilobase genomic deletion in one patient and skipped exon resulting in a frameshift and premature stop codon in the other. Complementation of patient cells with wild-type UBE2T restored efficient FANCD2 monoubiquitination and nuclear foci formation, and rescued the increased sensitivity to MMC-induced chromosome breakage.
PMID 26085575, 26119737
Describe the same individual with biallelic mutations in UBE2 and undertook Sanger sequencing of genomic DNA which identified two germline mutations, a paternal deletion and a maternal duplication of exons 2–6, both caused by aluY-mediated recombination events. Just as with the patients reported by Hira et al., retroviral complementation with wild-type UBE2T rescued the ICL-induced cell cycle arrest and chromosome breakage phenotypes (26046368, 26085575, 26119737)

Created: 22 Feb 2017, 5:29 p.m.

Comment on phenotypes: Added OMIM phenotype

Created: 22 Feb 2017, 12:26 p.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Fanconi anemia

Publications

• 26046368

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

Note that UBE2T is listed in the phenotypic series for Fanconi anemia in OMIM, but is not in the UKTGN gene panel for Fanconi anemia.

Created: 18 Oct 2016, 1:23 p.m.