Saquib A. Lakhani, MD
Associate Professor AdjunctCards
About
Research
Overview
Medical Research Interests
Congenital Abnormalities; Developmental Biology; Genetic Diseases, Inborn; Genetics; Genetics, Medical; Heart Defects, Congenital; Integrative Medicine; Pediatrics; Seizures
Publications
Featured Publications
A retrospective cohort analysis of the Yale pediatric genomics discovery program
Al‐Ali S, Jeffries L, Faustino EVS, Ji W, Mis E, Konstantino M, Zerillo C, Jiang Y, Spencer‐Manzon M, Bale A, Zhang H, McGlynn J, McGrath JM, Tremblay T, Brodsky NN, Lucas CL, Pierce R, Deniz E, Khokha MK, Lakhani SA. A retrospective cohort analysis of the Yale pediatric genomics discovery program. American Journal Of Medical Genetics Part A 2022, 188: 2869-2878. PMID: 35899841, PMCID: PMC9474639, DOI: 10.1002/ajmg.a.62918.Peer-Reviewed Original ResearchConceptsRetrospective cohort analysisNext-generation sequencingCohort analysisSystem abnormalitiesImmune system abnormalitiesCardiovascular system abnormalitiesFunctional molecular analysesNovel genesPrecise molecular diagnosisClinical characteristicsFurther genetic evaluationDiscovery programsComplex patientsMultisystem diseaseDisease genesPediatric providersRare genetic diseaseNew diagnosisPhenotype relationshipsPatientsGenetic diseasesMolecular analysisDiagnosisParticipant demographicsNGS resultsRethinking what constitutes a diagnosis in the genomics era: a critical illness perspective.
Lakhani SA, Pierce R. Rethinking what constitutes a diagnosis in the genomics era: a critical illness perspective. Current Opinion In Pediatrics 2019, 31: 317-321. PMID: 31090571, DOI: 10.1097/mop.0000000000000754.Peer-Reviewed Original ResearchConceptsPediatric intensivistsIll childrenCritical care pediatriciansFirst clinical diagnosisTypes of patientsWhole-exome sequencingSevere congenital diseaseUnderlying genetic causePatient's conditionIllness perspectiveUndiagnosed diseasePatientsDescriptive diagnosisClinical diagnosisCongenital diseaseGenetic testingGenetic abnormalitiesDiagnosisExome sequencingGenetic causeNext-generation sequencingClinical geneticistsIntensivistsGenetic diagnosisDiseaseDe novo pathogenic variants in neuronal differentiation factor 2 (NEUROD2) cause a form of early infantile epileptic encephalopathy
Sega AG, Mis EK, Lindstrom K, Mercimek-Andrews S, Ji W, Cho MT, Juusola J, Konstantino M, Jeffries L, Khokha MK, Lakhani SA. De novo pathogenic variants in neuronal differentiation factor 2 (NEUROD2) cause a form of early infantile epileptic encephalopathy. Journal Of Medical Genetics 2018, 56: 113. PMID: 30323019, DOI: 10.1136/jmedgenet-2018-105322.Peer-Reviewed Original ResearchConceptsEarly infantile epileptic encephalopathyInfantile epileptic encephalopathyEpileptic encephalopathyPatient variantsDe novo pathogenic variantsNovel de novo variantNovo pathogenic variantsEarly-onset refractory seizuresDifferentiation factor 2Whole-exome sequencingNeuronal differentiation factorRefractory seizuresSignificant developmental delaySpontaneous seizuresUnderlying etiologyEctopic neuronsDe novo variantsPatient's conditionEncephalopathyPathogenic variantsSevere disordersDevelopmental delayUnrelated childrenExome sequencingGene mutations
2025
A genetically modulated Toll-like receptor-tolerant phenotype in peripheral blood cells of children with multisystem inflammatory syndrome.
Khan R, Ji W, Guzman Rivera J, Madhvi A, Andrews T, Richlin B, Suarez C, Gaur S, Hasan U, Cuddy W, Singh A, Bukulmez H, Kaelber D, Kimura Y, Ganapathi U, Michailidis I, Ukey R, Moroso-Fela S, Kuster J, Casseus M, Roy J, Burns J, Kleinman L, Horton D, Lakhani S, Gennaro M. A genetically modulated Toll-like receptor-tolerant phenotype in peripheral blood cells of children with multisystem inflammatory syndrome. The Journal Of Immunology 2025 PMID: 40101747, DOI: 10.1093/jimmun/vkaf006.Peer-Reviewed Original ResearchToll-like receptorsLysosomal trafficking regulatorClinical laboratory indicatorsMIS-CMultisystem inflammatory syndromePeripheral blood cellsInflammatory syndromeLaboratory indicatorsHeterozygous carriersAgonists of Toll-like receptorsTLR responsesGut leakage markersDysregulated innate immune responseGenetic background of patientsBlood cells of childrenMIS-C patientsImmune response initiationIncreased plasma levelsNegative regulator of TLR signalingMIS-C childrenAssociated with hyperinflammationGenetic backgroundRegulator of TLR signalingBackground of patientsCells of childrenA single-cell atlas of circulating immune cells over the first 2 months of age in extremely premature infants
Olaloye O, Gu W, Gehlhaar A, Sabuwala B, Eke C, Li Y, Kehoe T, Farmer R, Gabernet G, Lucas C, Tsang J, Lakhani S, Taylor S, Tseng G, Kleinstein S, Konnikova L. A single-cell atlas of circulating immune cells over the first 2 months of age in extremely premature infants. Science Translational Medicine 2025, 17: eadr0942. PMID: 40043141, DOI: 10.1126/scitranslmed.adr0942.Peer-Reviewed Original ResearchConceptsExtremely premature infantsFull-term infantsT cellsMonths of lifePremature infantsImmune cellsMemory CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cellsMemory-like T cellsAnalysis of immune cellsNaive CD4<sup>+</sup>Peripheral T cell developmentWeeks of gestationCord blood samplesNatural killer cellsT helper 1B cell receptor sequencesT cell developmentCycling T cellsMonths of ageSingle-cell suspensionsAmount of bloodSusceptibility to infectionCD4<sup>+</sup>Killer cellsThe Alia Camel of Jordan: a genetically distinct dromedary breed
Haddad N, Al-Araishi M, Awabdeh S, Patidar R, Bell R, Jawasreh K, Alhurani H, Elharbid L, Sweidan R, Al-Anaswah E, Brake M, Sadder M, Blanco O, Sbeih L, Uduman M, Lakhani S, Khokha M, Weir A. The Alia Camel of Jordan: a genetically distinct dromedary breed. Journal Of Heredity 2025, esae076. PMID: 39761336, DOI: 10.1093/jhered/esae076.Peer-Reviewed Original Research
2024
Case report: Novel variants cause developmental and epileptic encephalopathy in three unrelated families from Mali
Bamba S, Sidibé L, Diallo S, Cissé L, Dembélé K, Yalcouyé A, Ji W, Dembélé M, Diarra S, Maiga A, Traoré O, Diallo S, Mefoung S, Touré A, Koné A, Jeffries L, Guinto C, Mis E, Fischbeck K, Khokha M, Lakhani S, Landouré G. Case report: Novel variants cause developmental and epileptic encephalopathy in three unrelated families from Mali. Frontiers In Genetics 2024, 15: 1412442. PMID: 39624497, PMCID: PMC11609193, DOI: 10.3389/fgene.2024.1412442.Peer-Reviewed Original ResearchWhole-exome sequencingGenetic basisIdentified rare variantsIn silico prediction analysisCompound heterozygous variantsPutative variantsIn silico toolsACMG criteriaExome sequencingProtein structureNovel variantsEpileptic encephalopathyAssess pathogenicityHeterozygous variantsRare variantsHomozygous variantSub-Saharan AfricaDisease mechanismsAssociated with earlier onsetRefractory to antiepileptic medicationsResistant to treatmentGroup of neurological disordersMalian familyEarly-onset seizuresPotential clinical implicationsGenetic profile of progressive myoclonic epilepsy in Mali reveals novel findings
Cissé L, Bamba S, Diallo S, Ji W, Dembélé M, Yalcouyé A, Coulibaly T, Traoré I, Jeffries L, Diarra S, Maiga A, Diallo S, Nimaga K, Touré A, Traoré O, Kotioumbé M, Mis E, Cissé C, Guinto C, Fischbeck K, Khokha M, Lakhani S, Landouré G. Genetic profile of progressive myoclonic epilepsy in Mali reveals novel findings. Frontiers In Neurology 2024, 15: 1455467. PMID: 39385815, PMCID: PMC11461190, DOI: 10.3389/fneur.2024.1455467.Peer-Reviewed Original ResearchWhole-exome sequencingACMG criteriaProgressive myoclonic epilepsyProtein 3D structuresHomozygous missense variantRecessive inheritance patternCADD scoresAutosomal recessive inheritance patternSequence variantsMissense variantsGenomic researchExome sequencingGenetic analysisGenetic studiesPathogenic variantsPedigree analysisGenetic epidemiologyGenetic researchGenetic profileHeterogeneous neurological disordersInheritance patternSporadic formsACMGGroup of neurological disordersMyoclonic epilepsyCC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow
Kim A, Sakin I, Viviano S, Tuncel G, Aguilera S, Goles G, Jeffries L, Ji W, Lakhani S, Kose C, Silan F, Oner S, Kaplan O, Group M, Ergoren M, Mishra-Gorur K, Gunel M, Sag S, Temel S, Deniz E. CC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow. Life Science Alliance 2024, 7: e202402708. PMID: 39168639, PMCID: PMC11339347, DOI: 10.26508/lsa.202402708.Peer-Reviewed Original ResearchConceptsDevelopmental disabilitiesIntellectual disabilityPatient-derived fibroblastsMidbrain regionsBrain developmentDefective ciliogenesisCSF circulationDisabilityCSF flowAbnormal CSF flowNervous system developmentMutant tadpolesCiliated tissuesMultiple model systemsVariant functionPronephric ductUnrelated familiesCC2D1AExpression patternsCiliogenesisRenal dysplasiaLeft-right organizerFunctional analysisDisease mechanismsBrainExome sequencing reveals genetic heterogeneity in consanguineous Pakistani families with neurodevelopmental and neuromuscular disorders
Bibi A, Ji W, Jeffries L, Zerillo C, Konstantino M, Mis E, Khursheed F, Khokha M, Lakhani S, Malik S. Exome sequencing reveals genetic heterogeneity in consanguineous Pakistani families with neurodevelopmental and neuromuscular disorders. American Journal Of Medical Genetics Part C Seminars In Medical Genetics 2024, 196: e32103. PMID: 39152716, DOI: 10.1002/ajmg.c.32103.Peer-Reviewed Original ResearchExome sequencingConsanguineous Pakistani familyDisease-causing genesFamily segregation analysisAssociated with phenotypesAffected individualsAccurate molecular diagnosisACMG criteriaCandidate variantsGenomic studiesPakistani familyGenomic researchGenetic heterogeneityNovel variantsSegregation analysisConsanguineous familyGenetic variantsNeurodevelopmental disordersHomozygous variantNeuromuscular disordersMiddle-income countriesMolecular diagnosisExomeES dataClinical phenotype
Clinical Trials
Current Trials
Pediatric Genomics Discovery Program (PGDP)
HIC ID1411014977RoleSub InvestigatorPrimary Completion Date12/31/2023Recruiting ParticipantsGenderBoth
News
News
- June 24, 2024Source: Yale News
Advanced Genetic Tools Help Researchers ID New Neurodevelopmental Syndrome
- March 25, 2024Source: OMIM
JEFFRIES-LAKHANI NEURODEVELOPMENTAL SYNDROME; JELANS
- July 26, 2023
2022-23 Department of Pediatrics Faculty Awards
- May 12, 2023
Yale Program Accepted Into NORD Rare Diseases Centers of Excellence Network
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