2024
Functional Evaluation of a Novel Homozygous ADCY3 Variant Causing Childhood Obesity
Mohammed I, Selvaraj S, Ahmed W, Al-Barazenji T, Dauleh H, Love D, Saraiva L, Hussain K. Functional Evaluation of a Novel Homozygous ADCY3 Variant Causing Childhood Obesity. International Journal Of Molecular Sciences 2024, 25: 11815. PMID: 39519366, PMCID: PMC11547096, DOI: 10.3390/ijms252111815.Peer-Reviewed Original ResearchAdenylate cyclase 3Early-onset obesityRegulating various downstream signaling pathwaysIn silico functional characterizationHomozygous nonsense variant c.Homozygous loss-of-function variantsIn silico functional analysisLoss-of-function variantsReceptor loss of functionNonsense variant c.Impaired enzymatic activityGene panel sequencingATP to cAMPIn silico validationDownstream signaling pathwaysGain-of-function variantsPrimary cilia of neuronsIn vitroInsulin resistanceLoss of functionTransmembrane proteinsFunctional characterizationPrimary ciliaNovel p.Variant c.Conserved genes regulating human sex differentiation, gametogenesis and fertilization
Fakhro K, Awwad J, Garibova S, Saraiva L, Avella M. Conserved genes regulating human sex differentiation, gametogenesis and fertilization. Journal Of Translational Medicine 2024, 22: 473. PMID: 38764035, PMCID: PMC11103854, DOI: 10.1186/s12967-024-05162-2.Peer-Reviewed Original ResearchConceptsFertility phenotypesReproductive biologyMechanisms of gene functionNewly-discovered genesHuman reproductive biologyCharacterization of genesLoss-of-function mutationsFundamental reproductive processesNext-generation sequencingGenome editing technologyConserved genesFunctional genomicsGene functionFunctional characterizationConsanguineous populationsSex differentiationGenesReproductive tissuesMonogenic causeMolecular mechanismsHuman reproductive tissuesEditing technologyReproductive processesPhenotypeFertility disorders
2023
Functional Characterization of Novel MC4R Variants Identified in Two Unrelated Patients with Morbid Obesity in Qatar
Mohammed I, Selvaraj S, Ahmed W, Al-Barazenji T, Hammad A, Dauleh H, Saraiva L, Al-Shafai M, Hussain K. Functional Characterization of Novel MC4R Variants Identified in Two Unrelated Patients with Morbid Obesity in Qatar. International Journal Of Molecular Sciences 2023, 24: 16361. PMID: 38003551, PMCID: PMC10671262, DOI: 10.3390/ijms242216361.Peer-Reviewed Original ResearchConceptsCREB signaling pathwaysHeterozygous variantsSignaling pathwayVariants associated with obesityIn silico prediction toolsEffects of allelic variationFunctional impactIn silico analysisMonogenic obesityDownstream signaling cascadesLigand binding activityGT1-7 cellsObesity-related genesIdentified variantsAllelic variationFunctional characterizationSilico analysisSanger sequencingPathogenic variantsActivation of PKALeptin-melanocortin pathwaySignaling cascadesMonogenic forms of obesityGenesIn vitro analysis