Imprinted genes in clinical exome sequencing: Review of 538 cases and exploration of mouse-human conservation in the identification of novel human disease loci.

Imprinted genes in clinical exome sequencing: Review of 538 cases and exploration of mouse-human conservation in the identification of novel human disease loci.
Eur J Med Genet. 2020 Mar 10;:103903
Authors: Bhoj EJ, Rajabi F, Baker SW, Santani A, Tan WH
Abstract
Human imprinting disorders cause a range of dysmorphic and neurocognitive phenotypes, and they may elude traditional molecular diagnosis such exome sequencing. The discovery of novel disorders related to imprinted genes has lagged behind traditional Mendelian disorders because current diagnostic technology, especially unbiased testing, has limited utility in their discovery. To identify novel imprinting disorders, we reviewed data for every human gene hypothesized to be imprinted, identified each mouse ortholog, determined its imprinting status in the mouse, and analyzed its function in humans and mice. We identified 17 human genes that are imprinted in both humans and mice, and have functional data in mice or humans to suggest that dysregulated expression would lead to an abnormal phenotype in humans. These 17 genes, along with known imprinted genes, were preferentially flagged 538 clinical exome sequencing tests. The identified genes were: DIRAS3 [1p31.3], TP73 [1p36.32], SLC22A3 [6q25.3], GRB10 [7p12.1], DDC [7p12.2], MAGI2 [7q21.11], PEG10 [7q21.3], PPP1R9A [7q21.3], CALCR [7q21.3], DLGAP2 [8p23.3], GLIS3 [9p24.2], INPP5F [10q26.11], ANO1 [11q13.3], SLC38A4 [12q13.11], GA...

Source: European Journal of Medical Genetics - March 9, 2020 Category: Genetics & Stem Cells Authors: Bhoj EJ, Rajabi F, Baker SW, Santani A, Tan WH Tags: Eur J Med Genet Source Type: research