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Research Article Summaries:

  • Kuechler et al. (2015)Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome

    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 SETD5 gene, 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

  • De Rubeis, S., et al. 2014. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature.
    In one of the largest whole exome studies to date, researchers analyzed 15,480 DNA samples—which included over 3,800 samples from individuals diagnosed with features of autism, intellectual disability, developmental delay, and/or other health concerns. By studying such large number of samples, the researchers were looking to identify new or undescribed genetic causes of autism.

    Of the 33 different genes identified in children with autism, 15 genes were already known to be associated with features of autism and have already been well described. Eleven “newer” genes were identified- SUV420H1, ADNP, BCL11A, CACNA2D3, CTTNBP2, CDC42BPB, APH1A, GABRB3, NR3C2, SETD5, and TRIO -  this study provides evidence that these genes are associated with the features of autism(because whole exome sequencing is a newer technology and our understanding of the genetic causes of autism is still growing, until now we had not seen a large enough number of children with changes in these genes to make any conclusions). In addition, seven other genes identified in this study are being described for the first time as autism risk genes: ASH1L, MLL3 (KMT2C), ETFB, NAA15, MUY9B, MIB1, and VIL1.

You can also visit SFARI's website to see information for researchers about this gene. SFARIgene: SETD5

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