Paediatric disorders - additional genes

Gene: DET1

Red List (low evidence)

Comment on publications: PMID: 39937864 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

Created: 26 Mar 2025, 5:15 p.m. | Last Modified: 26 Mar 2025, 5:15 p.m.

Panel Version: 6.15

PMID: 39937864 reports a family where the three affected siblings were homozygous for a variant in DET1 (c.76C>T, p.R26W) and also for a variant in COMMD4 (c.122T>G; p.L41R). These genes are both on chromosome 15, separated by 13 Mb and are likely to co-segregate. The parents of these cases were healthy, heterozygous carriers of the DET1 p.R26W variant. The cases described developed lethal developmental abnormalities and the longest lived sib died at 8 months old. Extensive functional studies were reported in PMID: 39937864 and using Det1-
deficient mice and human-induced pluripotent stem cells (iPSCs) expressing DET1R26W,
the authors were able to show that DET1 is essential for normal neuronal development.
Sources: Literature

Created: 26 Mar 2025, 5:03 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurological defects and lethality

Publications

• 39937864