2021
Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss
Richard EM, Bakhtiari S, Marsh APL, Kaiyrzhanov R, Wagner M, Shetty S, Pagnozzi A, Nordlie SM, Guida BS, Cornejo P, Magee H, Liu J, Norton BY, Webster RI, Worgan L, Hakonarson H, Li J, Guo Y, Jain M, Blesson A, Rodan LH, Abbott MA, Comi A, Cohen JS, Alhaddad B, Meitinger T, Lenz D, Ziegler A, Kotzaeridou U, Brunet T, Chassevent A, Smith-Hicks C, Ekstein J, Weiden T, Hahn A, Zharkinbekova N, Turnpenny P, Tucci A, Yelton M, Horvath R, Gungor S, Hiz S, Oktay Y, Lochmuller H, Zollino M, Morleo M, Marangi G, Nigro V, Torella A, Pinelli M, Amenta S, Husain RA, Grossmann B, Rapp M, Steen C, Marquardt I, Grimmel M, Grasshoff U, Korenke GC, Owczarek-Lipska M, Neidhardt J, Radio FC, Mancini C, Claps Sepulveda DJ, McWalter K, Begtrup A, Crunk A, Guillen Sacoto MJ, Person R, Schnur RE, Mancardi MM, Kreuder F, Striano P, Zara F, Chung WK, Marks WA, van Eyk CL, Webber DL, Corbett MA, Harper K, Berry JG, MacLennan AH, Gecz J, Tartaglia M, Salpietro V, Christodoulou J, Kaslin J, Padilla-Lopez S, Bilguvar K, Munchau A, Ahmed ZM, Hufnagel RB, Fahey MC, Maroofian R, Houlden H, Sticht H, Mane SM, Rad A, Vona B, Jin SC, Haack TB, Makowski C, Hirsch Y, Riazuddin S, Kruer MC. Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss. American Journal Of Human Genetics 2021, 108: 2006-2016. PMID: 34626583, PMCID: PMC8546233, DOI: 10.1016/j.ajhg.2021.08.003.Peer-Reviewed Original ResearchConceptsSensorineural hearing lossCerebral palsyHearing lossBi-allelic variantsInner earRodent inner earDevelopmental delay/intellectual disabilityThin corpus callosumGlial cell nucleiIntellectual disabilityRat hippocampal neuronsWhite matter volumeNeurosensory hair cellsPeriventricular leukomalaciaQuantitative volumetryCerebral volumeCorpus callosumHippocampal neuronsMatter volumeReceptor functionBrain imagingHair cellsProminent expressionNeurodevelopmental phenotypesAffected individualsThe genetic structure of the Turkish population reveals high levels of variation and admixture
Kars ME, Başak AN, Onat OE, Bilguvar K, Choi J, Itan Y, Çağlar C, Palvadeau R, Casanova JL, Cooper DN, Stenson PD, Yavuz A, Buluş H, Günel M, Friedman JM, Özçelik T. The genetic structure of the Turkish population reveals high levels of variation and admixture. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2026076118. PMID: 34426522, PMCID: PMC8433500, DOI: 10.1073/pnas.2026076118.Peer-Reviewed Original ResearchConceptsGenetic structureTR populationGenome-wide association studiesRuns of homozygosityGenomes Project populationsHigh inbreeding coefficientsDisease gene discoveryHigh-quality haplotypesPotential medical relevanceGene discoveryExtensive admixturePhenotypic consequencesWhole genomeGenetic basisInbreeding coefficientSpecific genesRare rangeGenome variantsAssociation studiesGenetic relationshipsFunctional consequencesWhole exomeSpecific phenotypesGenotype imputationMedical relevanceALG13 X‐linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes
Alsharhan H, He M, Edmondson AC, Daniel EJP, Chen J, Donald T, Bakhtiari S, Amor DJ, Jones EA, Vassallo G, Vincent M, Cogné B, Deb W, Werners AH, Jin SC, Bilguvar K, Christodoulou J, Webster RI, Yearwood KR, Ng BG, Freeze HH, Kruer MC, Li D, Raymond KM, Bhoj EJ, Sobering AK. ALG13 X‐linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. Journal Of Inherited Metabolic Disease 2021, 44: 1001-1012. PMID: 33734437, PMCID: PMC8720508, DOI: 10.1002/jimd.12378.Peer-Reviewed Original ResearchConceptsTransferrin glycosylationProtein glycosylationPathogenic variantsN-glycansGlycosylation analysisGlycosylationVariable clinical phenotypeALG13Novel variantsPlasma glycansPhenotypeCongenital disorderIonization quadrupole timeVariantsUnderlying mechanismClinical phenotypeIntellectual disabilityNovo c.Unreported subjectsInfantile spasmsEpileptic encephalopathyClinical dataGlycansMale subjectsNeurodevelopmental course
2020
A patient with mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, keratodermia syndrome caused by AP1B1 gene variant.
Meriç R, Ercan-Sencicek AG, Uludağ Alkaya D, Şahin Y, Sar M, Bilguvar K, Tüysüz B. A patient with mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, keratodermia syndrome caused by AP1B1 gene variant. Clinical Dysmorphology 2020, 30: 54-57. PMID: 32969855, DOI: 10.1097/mcd.0000000000000350.Peer-Reviewed Case Reports and Technical Notes
2019
Identification of a dominant MYH11 causal variant in chronic intestinal pseudo‐obstruction: Results of whole‐exome sequencing
Dong W, Baldwin C, Choi J, Milunsky JM, Zhang J, Bilguvar K, Lifton RP, Milunsky A. Identification of a dominant MYH11 causal variant in chronic intestinal pseudo‐obstruction: Results of whole‐exome sequencing. Clinical Genetics 2019, 96: 473-477. PMID: 31389005, DOI: 10.1111/cge.13617.Peer-Reviewed Original ResearchConceptsChronic Intestinal Pseudo-ObstructionSmooth muscle actin geneMuscle actin geneAdditional genetic evidenceGene burden analysisIntestinal Pseudo-ObstructionRare gastrointestinal disorderSmooth muscle contractionActin geneMyosin genesAdditional genesGenetic evidenceCausal variantsWhole-exome sequencingFamily membersCIPO patientsPseudo-ObstructionGenetic linkageGastrointestinal disordersDominant mutationsGenesUnaffected family membersGastrointestinal tractRare mutationsMuscle contraction
2018
De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias
Helbig KL, Lauerer RJ, Bahr JC, Souza IA, Myers CT, Uysal B, Schwarz N, Gandini MA, Huang S, Keren B, Mignot C, Afenjar A, de Villemeur T, Héron D, Nava C, Valence S, Buratti J, Fagerberg CR, Soerensen KP, Kibaek M, Kamsteeg EJ, Koolen DA, Gunning B, Schelhaas HJ, Kruer MC, Fox J, Bakhtiari S, Jarrar R, Padilla-Lopez S, Lindstrom K, Jin SC, Zeng X, Bilguvar K, Papavasileiou A, Xing Q, Zhu C, Boysen K, Vairo F, Lanpher BC, Klee EW, Tillema JM, Payne ET, Cousin MA, Kruisselbrink TM, Wick MJ, Baker J, Haan E, Smith N, Sadeghpour A, Davis EE, Katsanis N, Genomics T, Allori A, Angrist M, Ashley P, Bidegain M, Boyd B, Chambers E, Cope H, Cotten C, Curington T, Davis E, Ellestad S, Fisher K, French A, Gallentine W, Goldberg R, Hill K, Kansagra S, Katsanis N, Katsanis S, Kurtzberg J, Marcus J, McDonald M, Mikati M, Miller S, Murtha A, Perilla Y, Pizoli C, Purves T, Ross S, Sadeghpour A, Smith E, Wiener J, Corbett M, MacLennan A, Gecz J, Biskup S, Goldmann E, Rodan L, Kichula E, Segal E, Jackson K, Asamoah A, Dimmock D, McCarrier J, Botto L, Filloux F, Tvrdik T, Cascino G, Klingerman S, Neumann C, Wang R, Jacobsen J, Nolan M, Snell R, Lehnert K, Sadleir L, Anderlid B, Kvarnung M, Guerrini R, Friez M, Lyons M, Leonhard J, Kringlen G, Casas K, Achkar C, Smith L, Rotenberg A, Poduri A, Sanchis-Juan A, Carss K, Rankin J, Zeman A, Raymond F, Blyth M, Kerr B, Ruiz K, Urquhart J, Hughes I, Banka S, Study D, Hedrich U, Scheffer I, Helbig I, Zamponi G, Lerche H, Mefford H. De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias. American Journal Of Human Genetics 2018, 103: 666-678. PMID: 30343943, PMCID: PMC6216110, DOI: 10.1016/j.ajhg.2018.09.006.Peer-Reviewed Original ResearchConceptsR-type calcium currentsEpileptic encephalopathyCalcium currentPathogenic variantsDevelopmental impairmentR-type calcium channelsDe novo pathogenic variantsCause of DEEProfound developmental impairmentHyperkinetic movement disordersNovo pathogenic variantsAnti-epileptic drug topiramateCentral nervous systemAbundant epileptiform activityVoltage-gated CaSevere neurodevelopmental disorderSeizure freedomInfantile-onset seizuresIntractable seizuresEpileptiform activityVoltage-dependent activationMovement disordersSevere hypotoniaHuman epilepsySynaptic transmission