Limb disorders

Gene: UBA2

Green List (high evidence)

Additional report: 2x unrelated probands with isolated split hand malformation. fs variants - 1x de novo and 1x inherited from apparent unaffected mother (no radiographs of her hand available). 1x proband with unilateral split-hand malformation (missense). Her daughter and grandson reported to have ectrofactyly but were unavailable for testing

Created: 7 Aug 2021, 7:23 a.m. | Last Modified: 7 Aug 2021, 7:23 a.m.

Panel Version: 2.49

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Split hand malformation

Publications

• 34159400

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 30 Jan 2023, 1:37 p.m. | Last Modified: 30 Jan 2023, 1:37 p.m.

Panel Version: 3.6

Comment on list classification: Leaving rating as amber for now, but with a recommendation for green rating following GMS review. There are now 5 cases reported with split hand malformation and plausible disease causing variants in this gene.

Created: 10 Oct 2021, 2:36 p.m. | Last Modified: 10 Oct 2021, 2:36 p.m.

Panel Version: 2.60

As reviewer notes, in PMID: 34159400 (Elsner et al 2021) they report 3 unrelated cases where a variant in UBA2 are reported in individuals with split hand malformation.

Created: 10 Oct 2021, 2:34 p.m. | Last Modified: 10 Oct 2021, 2:34 p.m.

Panel Version: 2.58

Comment on list classification: Promoting this gene from red to amber as there are 2 cases with variants in this gene and ectrodactyly reported. Also currently on the Skeletal dysplasia panel as amber.

Created: 20 Jan 2021, 6:01 p.m. | Last Modified: 20 Jan 2021, 6:01 p.m.

Panel Version: 2.31

Two reports of SNV in UBA2 in patients with split-hand/foot malformation. There are also reports of microdeletions including the UBA2 gene in 2 patients with split-hand/foot malformation/ectrodactyly

PMID: 31332306 - Yamoto et al 2019 - report one Japanese patient (38-II-1) with split-hand/foot malformation and a de novo c.1324dupT p.(Tyr442Leufs17) variant in UBA2 was found by exome sequencing. Not found in gnomAD. The UBA2 gene was considered a candidate gene because deletion of the region containing this gene (19q13.11) was found in a SHFM patient in this study using aCGH (patient 26-II-3) and in two other studies where microdeletions encompassing the UBA2 gene (among many other genes) were found in singular patients with ectrodactyly; PMID: 24243649 Chowdhury et al 2013 and PMID: 29988626 Abe et al 2019.

PMID: 31587267 - mother and son with aplasia cutis congenita. The son also has bilateral ectrodactyly, a horseshoe kidney, low‐lying conus medullaris and tracheo‐oesophageal fistula. WES identified a heterozygous deletion at c.327delT of UBA2, which leads to a frameshift and early top codon, in both the son and his mother.
Sources: Literature

Created: 20 Jan 2021, 5:51 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
split hand-foot malformation MONDO:0016576; aplasia cutis congenita (disease) MONDO:0007145; ectrodactyly

Publications

• 31332306
• 24243649
• 29988626
• 31587267
• 34159400