Salpietro, V, Dixon CL, Guo H, Bello OD, Vandrovcova J, Efthymiou S, Maroofian R, Heimer G, Burglen L, Valence S et al..
2019.
AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders, 2019. Nature Communications. 10(1)
AbstractAMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission.
Sorsa, T, Gursoy UK, Nwhator SO, Hernandez M, Tervahartiala T, Leppilahti J, Gursoy M, Könönen E, Emingil G, Pussinen PJ, Mäntylä P.
Submitted.
Analysis of matrix metalloproteinases, especially MMP-8. in gingival crevicular fluid, mouthrinse and saliva for monitoring periodontal diseases. 70:142–163., Number 1
Abstractn/a
Akinyemi, R, Tiwari HK, Arnett DK, Ovbiagele B, Irvin MR, Wahab K, Sarfo F, Srinivasasainagendra V, Adeoye A, Perry RT, Akpalu A, Jenkins C, Arulogun O, Gebregziabher M, Owolabi L, Obiako R, Sanya E, Komolafe M, Fawale M, Adebayo P, Osaigbovo G, Sunmonu T, Olowoyo P, Chukwuonye I, Obiabo Y, Onoja A, Akinyemi J, Ogbole G, Melikam S, Saulson R, Owolabi M.
2018.
APOL1, CDKN2A/CDKN2B, and HDAC9 polymorphisms and small vessel ischemic stroke, 2018. Acta Neurologica Scandinavica. 137(1)
AbstractObjective: Worldwide, the highest frequencies of APOL1-associated kidney variants are found in indigenous West Africans among whom small vessel disease (SVD) ischemic stroke is the most common stroke phenotype. The objective of this study was to investigate the association and effect sizes of 23 selected SNPs in 14 genes of relevance, including the APOL1 G1 variants, with the occurrence of SVD ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. Materials and Methods: Cases were consecutively recruited consenting adults (aged 18 years or older) with neuroimaging—confirmed first clinical stroke. Stroke-free controls were ascertained using a locally validated version of the Questionnaire for Verifying Stroke-Free Status (QVSFS). Logistic regression models adjusting for known vascular risk factors were fitted to assess the associations of the 23 SNPs in rigorously phenotyped cases (N = 154) of SVD ischemic stroke and stroke-free (N = 483) controls. Results: Apolipoprotein L1 (APOL1) rs73885319 (OR = 1.52; CI: 1.09-2.13, P-value =.013), rs2383207 in CDKN2A/CDKN2B (OR = 3.08; CI: 1.15-8.26, P –value =.026) and rs2107595 (OR = 1.70; CI: 1.12-2.60, P-value =.014) and rs28688791 (OR = 1.52; CI: 1.03-2.26, P-value =.036) in HDAC9 gene were associated with SVD stroke at 0.05 significance level. Polymorphisms in other genes did not show significant associations. Conclusion: This is the first report of a specific association of APOL1 with a stroke subtype. Further research is needed to confirm these initial findings and deepen understanding of the genetics of stroke in people of African ancestry with possible implications for other ancestries as all humans originated from Africa.
L.J.J, G, W.L A, M E, P.A M, T B, B A, P D, F.K.N A, S.A B, A M, M L, E.A A-A, W D, P T, O J, M D, P A, A.A O, R B, G P-R, M G, S O-Y, G.O O, P.B O, L A-R, F A, T H, P G, M.O O, C.J B, M.L M, A.A A, J.C M, A B.
2016.
Association studies and direct DNA sequencing implicate genetic susceptibility loci in the etiology of nonsyndromic orofacial clefts in sub-Saharan African populations. J Dental Research. 95(11):1245-1256.