Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome

Original research article by A. Kuechler et al. (2015).

Read the article here.

Through whole-exome sequencing (WES) of 250 patients with unexplained intellectual disability (ID) and their parents, this research team identified two patients with variants (changes or alterations in the DNA sequence) of the SETD5 gene. These variants were de novo, meaning that this genetic change was not found in either parent’s DNA. Four additional patients were identified with de novo microdeletions involving SETD5 (small portions of the chromosome which include the SETD5 gene are missing, or deleted). These microdeletions may vary in size, and can affect not only the SETD5gene, but neighboring portions of the DNA. Click here for more information on different types of genetic changes. Clinical features for these 6 patients were reported and summarized by Kuechler et al. Ranging from age 1 to age 20, the observed features in the 6 individuals found to have a SETD5 mutation or microdeletion are summarized below. In this group of children and young adults with intellectual disability, all 6 individuals had speech delay and differences in their facial features. Features for individuals with the microdeletion may be more severe because, depending on the exact size and location of the deletion, these individuals had 3 to 70 other genes missing, in addition to SETD5.