Ichthyosis and erythrokeratoderma
Gene: DBR1
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
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: LiteratureCreated: 7 Sep 2023, 7:07 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Ichthyosis (MONDO#0019269), DBR1-related
Publications
Gene: dbr1 has been classified as Amber List (Moderate Evidence).
Tag founder-effect tag was added to gene: DBR1.
Gene: dbr1 has been removed from the panel.
Phenotypes for gene: DBR1 were changed from Ichthyosis (MONDO#0019269), DBR1-related to ichthyosis, MONDO:0019269
gene: DBR1 was added gene: DBR1 was added to Ichthyosis and erythrokeratoderma. Sources: Literature Mode of inheritance for gene: DBR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DBR1 were set to 37656279 Phenotypes for gene: DBR1 were set to Ichthyosis (MONDO#0019269), DBR1-related Review for gene: DBR1 was set to AMBER