A DNA repair disorder caused by de novo monoallelic DDB1 variants is associated with a neurodevelopmental syndrome

The DNA damage-binding protein 1 (DDB1) is part of the CUL4 –DDB1 ubiquitin E3 ligase complex (CRL4), which is essential for DNA repair, chromatin remodeling, DNA replication, and signal transduction. Loss-of-function variants in genes encoding the complex components CUL4 and PHIP have been reported to cause syndromic intellectual disability with hypotonia and obesity, but no phenotype has been reported in association with DDB1 variants. Here, we report eight unrelated individuals, identified through Matchmaker Exchange, with de novo monoallelic variants in DDB1, including one recurrent variant in four individuals.

Source: The American Journal of Human Genetics - March 19, 2021 Category: Genetics & Stem Cells Authors: Susan M. White, Elizabeth Bhoj, Christoffer Nell åker, Augusta M.A. Lachmeijer, Aren E. Marshall, Kym M. Boycott, Dong Li, Wendy Smith, Taila Hartley, Arran McBride, Michelle E. Ernst, Alison S. May, Dagmar Wieczorek, Rami Abou Jamra, Margarete Koch-Hogr Tags: Report Source Type: research