Genes in panel
Regions in panel
Prev Next

Intellectual disability

Gene: DDB1

Amber List (moderate evidence)

DDB1 (damage specific DNA binding protein 1)
EnsemblGeneIds (GRCh38): ENSG00000167986
EnsemblGeneIds (GRCh37): ENSG00000167986
OMIM: 600045, Gene2Phenotype
DDB1 is in 5 panels

1 review

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is enough evidence to promote this gene to Green at the next review - sufficient unrelated cases (8) presenting consistent features primarily characterised by ID/DD and hypotonia, supported by functional data (PMID:33743206)
Created: 30 Mar 2021, 2:34 p.m. | Last Modified: 30 Mar 2021, 2:34 p.m.
Panel Version: 3.983
- PMID: 33743206 (2021) - 8 unrelated individuals with de novo variants in DDB1, including one recurrent variant in four individuals (c.637G>A, p.Glu213Lys) and two different substitutions at the same amino acid residue (p.Arg188Trp and p.Arg188Gln). Clinical features were consistent and include hypotonia (7/8) and mild-moderate developmental delay or intellectual disability (8/8) and similar facial gestalt. Brachydactyly was common and most noticeable in the feet (6/8), and two individuals had cutaneous toe syndactyly. All three older individuals had a BMI in the obese range for their age. Functional studies using patient-derived lymphoblasts showed altered DDB1 function resulting in abnormal DNA damage signatures and histone methylation following UV-induced DNA damage.

Variants in other CRL4 complex components, such as CUL4B (MIM# 300304) and PHIP (MIM# 612870), have been shown to cause overlapping phenotypes consisting of syndromic ID with hypotonia and obesity.
Sources: Literature
Created: 30 Mar 2021, 2:24 p.m. | Last Modified: 30 Mar 2021, 2:32 p.m.
Panel Version: 3.982

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

Phenotypes
Intellectual disability

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Intellectual disability
Tags
Q2_21_rating
OMIM
600045
Clinvar variants
Variants in DDB1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

30 Mar 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: ddb1 has been classified as Amber List (Moderate Evidence).

30 Mar 2021, Gel status: 1

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: DDB1.

30 Mar 2021, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Arina Puzriakova (Genomics England Curator)

gene: DDB1 was added gene: DDB1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: DDB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: DDB1 were set to 33743206 Phenotypes for gene: DDB1 were set to Intellectual disability Review for gene: DDB1 was set to GREEN