Ichthyosis and erythrokeratoderma

Gene: DBR1

I don't know

Comment on list classification: As reviewed by Zornitza Stark, the same variant was identified in four different families and haplotype analysis suggests this to be a founder variant. There is functional data available. This gene can only be rated amber with the current evidence.

The 'founder-effect' tag is added to this gene.

Created: 10 Apr 2024, 8:25 p.m. | Last Modified: 10 Apr 2024, 8:26 p.m.

Panel Version: 3.27

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
ichthyosis, MONDO:0019269

I don't know

PMID: 37656279:
- A homozygous missense as a founder recessive DBR1 variant in four consanguineous families.
- Total of 7 affected children. WES done for one proband from each family.
- Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life.
- RNA and protein studies using fibroblasts derived from a patient are supportive of pathogenicity: RNA-seq, rt-qPCR and western blotting, showing marked reduction of DBR1 level and intronic RNA lariat accumulation in the patient sample.
- Haplotype analysis revealed that the four families all share a haplotype extending at least 2.27 Mb around the c.200A>G p.(Tyr67Cys) DBR1 founder variant.
- Authors proposed this is a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility, and highlighted the apparent lack of correlation with the degree of DBR1 deficiency.
Sources: Literature

Created: 7 Sep 2023, 7:07 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ichthyosis (MONDO#0019269), DBR1-related

Publications

• 37656279