2025
Biallelic variants in the conserved ribosomal protein chaperone gene PDCD2 are associated with hydrops fetalis and early pregnancy loss
Landry-Voyer A, Holling T, Mis E, Hassani Z, Alawi M, Ji W, Jeffries L, Kutsche K, Bachand F, Lakhani S. Biallelic variants in the conserved ribosomal protein chaperone gene PDCD2 are associated with hydrops fetalis and early pregnancy loss. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2426078122. PMID: 40208938, PMCID: PMC12012559, DOI: 10.1073/pnas.2426078122.Peer-Reviewed Original ResearchConceptsRibosomal RNA processingRNA processingNonimmune hydrops fetalisRibosomal biogenesis disordersNext generation sequencingRibosome biogenesisPregnancy lossPatient variantsMolecular chaperonesExome sequencingGeneration sequencingPDCD2Biallelic variantsGenetic variantsHydrops fetalisIndependent familiesIn vivo approachesAffected fetusMolecular causesPrimary fibroblastsDevelopmental defectsMonogenic disordersAssociated with hydrops fetalisUS5Early pregnancy lossPhysiologic mechanisms underlying polycystic kidney disease
Boletta A, Caplan M. Physiologic mechanisms underlying polycystic kidney disease. Physiological Reviews 2025, 105: 1553-1607. PMID: 39938884, PMCID: PMC12174308, DOI: 10.1152/physrev.00018.2024.Peer-Reviewed Original ResearchPrimary ciliaPolycystic kidney diseaseTrafficking of proteinsHuman ciliopathiesExtracellular signalsMultiple genesKidney diseaseProtein productionMolecular basisCell biologyMonogenic disordersCyst formationGenesRenal epithelial cellsProteinCiliaBiochemical informationApical surfaceEpithelial cellsFunctional expressionPhysiological propertiesWealth of informationPhysiological mechanismsCellsFibrocystin
2024
Advancing Genetic Testing in Kidney Diseases: Report From a National Kidney Foundation Working Group
Franceschini N, Feldman D, Berg J, Besse W, Chang A, Dahl N, Gbadegesin R, Pollak M, Rasouly H, Smith R, Winkler C, Gharavi A, Group N, Ars E, Bekheirnia M, Bier L, Bleyer A, Fuller L, Halbritter J, Harris P, Kiryluk K, Knoers N, Kopp J, Kramer H, Lagas S, Lieske J, Lu W, Mannon R, Markowitz G, Moe O, Nadkarni G, Nast C, Parekh R, Pei Y, Reed K, Rehm H, Richards D, Roberts M, Sabatello M, Salant D, Sampson M, Sanna-Cherchi S, Santoriello D, Sedor J, Sneddon T, Watnick T, Wilfond B, Williams W, Wong C. Advancing Genetic Testing in Kidney Diseases: Report From a National Kidney Foundation Working Group. American Journal Of Kidney Diseases 2024, 84: 751-766. PMID: 39033956, PMCID: PMC11585423, DOI: 10.1053/j.ajkd.2024.05.010.Peer-Reviewed Original ResearchGenetic testingAllied health professionalsImplementation of genetic testingModified Delphi processChronic kidney diseaseScreening of kidney diseasesHealth professionalsWorking GroupKidney diseaseGenetic risk factorsDelphi processWorking group of expertsNational Kidney FoundationPolygenic causeDisease of multiple causesClinical decisionsRisk factorsGroup of expertsCause of kidney diseaseKidney FoundationGenetic basisMultiple causesGroup consensusGenetic causeMonogenic disorders
2023
When Development of the Alveolar Gas Exchange Unit Fails: Universal Single-Cell Lessons from Rare Monogenic Disorders
Schupp J, Kaminski N. When Development of the Alveolar Gas Exchange Unit Fails: Universal Single-Cell Lessons from Rare Monogenic Disorders. American Journal Of Respiratory And Critical Care Medicine 2023, 208: 652-654. PMID: 37555730, PMCID: PMC10515565, DOI: 10.1164/rccm.202307-1271ed.Commentaries, Editorials and LettersThe C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion
Onuchic L, Padovano V, Schena G, Rajendran V, Dong K, Shi X, Pandya R, Rai V, Gresko N, Ahmed O, Lam T, Wang W, Shen H, Somlo S, Caplan M. The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion. Nature Communications 2023, 14: 1790. PMID: 36997516, PMCID: PMC10063565, DOI: 10.1038/s41467-023-37449-1.Peer-Reviewed Original ResearchConceptsPolycystin-1Nicotinamide nucleotide transhydrogenaseTerminal tailCystic phenotypeAutosomal dominant polycystic kidney diseaseCyst cell proliferationC-terminal domainAmino acid residuesLethal monogenic disorderC-terminal cleavageNucleotide transhydrogenaseAcid residuesMitochondrial functionTransgenic expressionPKD1 geneRedox stateShort fragmentsCell proliferationMonogenic disordersDominant polycystic kidney diseasePolycystic kidney diseaseGene therapy strategiesProteinPhenotypeFragmentsGenomic analysis of lean individuals with NAFLD identifies monogenic disorders in a prospective cohort study
Zheng M, Huang D, Konkwo C, Agrawal S, Khera A, Loomba R, Vilarinho S, Ajmera V. Genomic analysis of lean individuals with NAFLD identifies monogenic disorders in a prospective cohort study. JHEP Reports 2023, 5: 100692. PMID: 36937991, PMCID: PMC10017416, DOI: 10.1016/j.jhepr.2023.100692.Peer-Reviewed Original ResearchNon-alcoholic fatty liver diseaseLean non-alcoholic fatty liver diseaseFatty liver diseaseBiopsy-proven non-alcoholic fatty liver diseaseLiver diseaseWhole-exome sequencingLean patientsVisceral adiposityPatient 2Liver fatLean individualsMonogenic disordersMagnetic Resonance Imaging AssessmentExome sequencingHigh liver fatProspective cohort studyCohort of patientsEvaluation of patientsHereditary fructose intoleranceHomozygous pathogenic mutationNAFLD subtypesUnique genetic mutationsCohort studyLiver biopsyRare heterozygous mutations
2022
Inhibition of MEK-ERK signaling reduces seizures in two mouse models of tuberous sclerosis complex
Nguyen LH, Leiser SC, Song D, Brunner D, Roberds SL, Wong M, Bordey A. Inhibition of MEK-ERK signaling reduces seizures in two mouse models of tuberous sclerosis complex. Epilepsy Research 2022, 181: 106890. PMID: 35219048, PMCID: PMC8930622, DOI: 10.1016/j.eplepsyres.2022.106890.Peer-Reviewed Original ResearchConceptsTuberous sclerosis complexMouse modelTSC mouse modelsDevelopmental brain malformationsMEK-ERKNovel treatment targetsMEK inhibitor PD0325901Intractable epilepsySeizure activityTSC patientsSeizure suppressionBrain malformationsMTOR inhibitorsTreatment targetsMEK-ERK activitySeizuresTSC neuropathologyPotential alternative strategyMEK-ERK inhibitionInhibitor PD0325901Monogenic disordersInhibitionMTORTreatmentEverolimus
2020
Analysis of GWAS-Derived Schizophrenia Genes for Links to Ischemia-Hypoxia Response of the Brain
Schmidt-Kastner R, Guloksuz S, Kietzmann T, van Os J, Rutten B. Analysis of GWAS-Derived Schizophrenia Genes for Links to Ischemia-Hypoxia Response of the Brain. Frontiers In Psychiatry 2020, 11: 393. PMID: 32477182, PMCID: PMC7235330, DOI: 10.3389/fpsyt.2020.00393.Peer-Reviewed Original ResearchObstetric complicationsIschemia-hypoxiaHypoxia-inducible factorNervous systemSynaptic functionMonogenic disordersFocal brain ischemiaGenome-wide association studiesChi-square testSCZ genesEarly brain developmentBrain ischemiaMental disordersMutation-intolerant genesBrain developmentSCZ genome-wide association studySynaptic genesDisordersBh geneSchizophreniaBrainGene setsResponse genesSchizophrenia genesSubsetSubacute Neuropsychiatric Syndrome in Girls With SHANK3 Mutations Responds to Immunomodulation
Bey AL, Gorman MP, Gallentine W, Kohlenberg TM, Frankovich J, Jiang YH, Van Haren K. Subacute Neuropsychiatric Syndrome in Girls With SHANK3 Mutations Responds to Immunomodulation. 2020, 145: e20191490. PMID: 32015180, PMCID: PMC7802010, DOI: 10.1542/peds.2019-1490.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAggressionAntipsychotic AgentsAnxietyAutism Spectrum DisorderCatatoniaChildCompulsive BehaviorCryingDevelopmental DisabilitiesFemaleFrameshift MutationHallucinationsHumansImmunoglobulins, IntravenousImmunosuppressive AgentsImmunotherapyIrritable MoodMethylprednisoloneMutismNerve Tissue ProteinsNeuroprotective AgentsObsessive-Compulsive DisorderRecurrenceSelf CareSleep Initiation and Maintenance DisordersStereotyped BehaviorSyndromeUrinary IncontinenceUrinary RetentionConceptsClinical observationsChronic relapsing coursePeriod of treatmentYears of ageImmunomodulatory treatmentUrinary retentionRelapsing courseNeurologic regressionCase seriesAntipsychotic medicationNeuropsychiatric syndromeMood disordersImmune functionObsessive-compulsive behaviorRare monogenic disordersNeurobehavioral syndromeTranslational investigationsPremorbid levelSHANK3 mutationsPatientsHormonal stimuliMonogenic disordersResponsive phenotypeDevelopmental disabilitiesSyndrome
2018
In utero nanoparticle delivery for site-specific genome editing
Ricciardi AS, Bahal R, Farrelly JS, Quijano E, Bianchi AH, Luks VL, Putman R, López-Giráldez F, Coşkun S, Song E, Liu Y, Hsieh WC, Ly DH, Stitelman DH, Glazer PM, Saltzman WM. In utero nanoparticle delivery for site-specific genome editing. Nature Communications 2018, 9: 2481. PMID: 29946143, PMCID: PMC6018676, DOI: 10.1038/s41467-018-04894-2.Peer-Reviewed Original ResearchConceptsSite-specific genome editingReversal of splenomegalyPeptide nucleic acidIntra-amniotic administrationBlood hemoglobin levelsMonogenic disordersNanoparticle deliveryPolymeric nanoparticlesPostnatal elevationGestational ageHemoglobin levelsImproved survivalPediatric morbidityDisease improvementHuman β-thalassemiaReticulocyte countNormal organ developmentMouse modelNormal rangeEarly interventionGenome editingOff-target mutationsPostnatal growthGene editingVersatile methodAssisted Reproductive Technology and Origins of Disease: The Clinical Realities and Implications
Morin SJ, Seli E. Assisted Reproductive Technology and Origins of Disease: The Clinical Realities and Implications. Seminars In Reproductive Medicine 2018, 36: 195-203. PMID: 30866006, DOI: 10.1055/s-0038-1677048.Peer-Reviewed Original ResearchConceptsSevere male factor infertilityART-exposed childrenLow birth weightMale factor infertilityReproductive technologiesSevere monogenic disordersAssisted Reproductive TechnologyMultiple gestationsSubfertile womenFactor infertilityMetabolic derangementsPremature birthAbsolute riskBirth weightCardiovascular diseaseAdditional diagnosisNumber of womenClinical realityMultiple studiesMonogenic disordersNumber of couplesRiskOrigin of diseaseDiseaseWomen
2014
Polycystin-1: a master regulator of intersecting cystic pathways
Fedeles SV, Gallagher AR, Somlo S. Polycystin-1: a master regulator of intersecting cystic pathways. Trends In Molecular Medicine 2014, 20: 251-260. PMID: 24491980, PMCID: PMC4008641, DOI: 10.1016/j.molmed.2014.01.004.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseaseAutosomal recessive polycystic kidney diseaseAutosomal dominant polycystic liver diseasePolycystic kidney diseaseKidney diseasePolycystic liver diseaseRecessive polycystic kidney diseaseDominant polycystic kidney diseaseLiver diseasePolycystic diseaseCyst growthLethal monogenic disorderCyst formationTranslational implicationsDiseaseMonogenic disordersCausative genesCystic phenotypeRecent dataPolycystin-1Polycystin-2Master regulator
2013
Primary dystonias and genetic disorders with dystonia as clinical feature of the disease
Moghimi N, Jabbari B, Szekely AM. Primary dystonias and genetic disorders with dystonia as clinical feature of the disease. European Journal Of Paediatric Neurology 2013, 18: 79-105. PMID: 23911094, DOI: 10.1016/j.ejpn.2013.05.015.Peer-Reviewed Original ResearchConceptsPrimary dystoniaClinical featuresSustained muscle contractionsCharacteristic clinical featuresClinical entityAbnormal postureMovement disordersDystoniaClinical practiceClinical phenomenologyAdvances of geneticsGenetic syndromesMuscle contractionRepetitive movementsUnderlining etiologiesDisordersCommon formMonogenic disordersGenetic disordersMolecular underpinningsDetailed searchMendelian disordersComplex casesLarge groupSyndrome
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