ELMO Domain Containing 1 (ELMOD1) Gene Mutation Is Associated with Mental Retardation and Autism Spectrum Disorder
ELMO domain containing 1 (ELMOD1) encodes a protein with GTPase-activating functions. Previous studies have confirmed its overexpression in brain tissues. Although no previous study has reported mutations in this gene in human subjects, spontaneous inactivating mutations in the mouse homolog of this gene have been associated with deafness and balance problems. In the current study, we have performed whole exome sequencing (WES) in a patient with intellectual disability. We found a novel mutation in ELMOD1 gene (c.571delG, p.D191MfsTer25) in the proband and two other affected cases in the family. Segregation analysis showed that parents carried the mutation in the heterozygote state. Consequently, the current study reports the first case of mutation in ELMOD1 in human subjects and demonstrates the significant difference in the phenotypes associated with ELMOD1 mutations in humans and mice.
KeywordsELMO domain containing 1 ELMOD1 Intellectual disability
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, Habuka M, Tahmasebpoor S, Danielsson A, Edlund K, Asplund A, Sjöstedt E, Lundberg E, Szigyarto CAK, Skogs M, Takanen JO, Berling H, Tegel H, Mulder J, Nilsson P, Schwenk JM, Lindskog C, Danielsson F, Mardinoglu A, Sivertsson Å, von Feilitzen K, Forsberg M, Zwahlen M, Olsson IM, Navani S, Huss M, Nielsen J, Ponten F, Uhlén M (2014) Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics 13:397–406. https://doi.org/10.1074/mcp.M113.035600 CrossRefGoogle Scholar
- Grimsley CM, Kinchen JM, Tosello-Trampont AC, Brugnera E, Haney LB, Lu M, Chen Q, Klingele D, Hengartner MO, Ravichandran KS (2004) Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration. J Biol Chem 279:6087–6097. https://doi.org/10.1074/jbc.M307087200 CrossRefGoogle Scholar
- Jackson CL, Bouvet S (2014) Arfs at a glance. The Company of Biologists Ltd. J Cell Sci 127: Pt 19:4103–9. doi: https://doi.org/10.1242/jcs.14489910.1242/jcs.144899
- Steffen A, Ladwein M, Dimchev GA, Hein A, Schwenkmezger L, Arens S, Ladwein KI, Holleboom JM, Schur F, Small JV, Schwarz J, Gerhard R, Faix J, Stradal TEB, Brakebusch C, Rottner K (2013) Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation. J Cell Sci 126:4572–4588. https://doi.org/10.1242/jcs.118232 CrossRefGoogle Scholar
- Zamboni V, Jones R, Umbach A, Ammoni A, Passafaro M, Hirsch E, Merlo GR (2018) Rho GTPases in intellectual disability: from genetics to therapeutic opportunities. Int J Mol Sci 19. https://doi.org/10.3390/ijms19061821