Ataxia - paediatric

Gene: DAB1

Red List (low evidence)

Single individual reported with bi-allelic variants, note this is a distinct mechanism to the repeat expansion in this gene which is associated with disease.

Created: 4 Oct 2021, 7:11 a.m. | Last Modified: 4 Oct 2021, 7:11 a.m.

Panel Version: 0.292

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ataxia; Intellectual disability

I don't know

WES trio analysis identified compound heterozygous DAB1 canonical splice variants in a child with epilepsy (onset 6 years), developmental delay, cerebellar ataxia, oral motor difficulty, and structural brain abnormalities. RT-PCR confirms that the first variant (c.307-2A>T) causes a in-frame deletion of 3 amino acids. The second variant (c.67+1G>T) is reported to causes an in-frame deletion of exon 4 (first coding exon) and loss of the ATG initiation site.
Sources: Literature

Created: 4 Oct 2021, 5:54 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
epilepsy; developmental delay; cerebellar ataxia; structural brain abnormalities; oral motor difficulty

Publications

• PMID: 33928188

Green List (high evidence)

Comment on list classification: Note: the pentanucleotide repeat is the only cause of ataxia for this gene, which is not detected by current WES/WGS technologies.

Created: 18 Apr 2020, 7:20 a.m. | Last Modified: 18 Apr 2020, 7:20 a.m.

Panel Version: 0.48

In 35 affected individuals from 3 large, multigenerational kindreds from southern Portugal with ataxia had expansion of a heterozygous 5-bp ATTTC(n) insertion in the 5-prime UTR intron 3 of the DAB1 gene.
Sources: Expert list

Created: 18 Apr 2020, 7:19 a.m.

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

Phenotypes
Spinocerebellar ataxia 37 MIM#615945

Publications

• 28686858

Mode of pathogenicity
Other