2021
Prenatal exome sequencing and chromosomal microarray analysis in fetal structural anomalies in a highly consanguineous population reveals a propensity of ciliopathy genes causing multisystem phenotypes
Al-Hamed M, Kurdi W, Khan R, Tulbah M, AlNemer M, AlSahan N, AlMugbel M, Rafiullah R, Assoum M, Monies D, Shah Z, Rahbeeni Z, Derar N, Hakami F, Almutairi G, AlOtaibi A, Ali W, AlShammasi A, AlMubarak W, AlDawoud S, AlAmri S, Saeed B, Bukhari H, Ali M, Akili R, Alquayt L, Hagos S, Elbardisy H, Akilan A, Almuhana N, AlKhalifah A, Abouelhoda M, Ramzan K, Sayer J, Imtiaz F. Prenatal exome sequencing and chromosomal microarray analysis in fetal structural anomalies in a highly consanguineous population reveals a propensity of ciliopathy genes causing multisystem phenotypes. Human Genetics 2021, 141: 101-126. PMID: 34853893, DOI: 10.1007/s00439-021-02406-9.Peer-Reviewed Original ResearchMeSH KeywordsChromosome AberrationsCiliopathiesCohort StudiesConsanguinityExome SequencingFemaleFetusGenetic Predisposition to DiseaseGenetic TestingGenetic VariationHumansMicroarray AnalysisPhenotypePregnancyPrenatal DiagnosisConceptsChromosomal microarray analysisExome sequencingConsanguineous populationsFetal anomaliesMicroarray analysisHeterozygous de novo pathogenic variantLoss of function variantsFetal phenotypeParental DNA samplesFetal abnormalitiesDiagnostic yieldMolecular genetic defectMolecular genetic diagnosticsHistory of congenital anomaliesPrenatal exome sequencingVariable diagnostic yieldCiliopathy genesFetal structural anomaliesMolecular genetic abnormalitiesStructural anomaliesCiliopathy disordersCiliopathy syndromesFunctional variantsNovel variantsGenetic diagnosticsExpanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann‐Steiner syndrome
Sheppard S, Campbell I, Harr M, Gold N, Li D, Bjornsson H, Cohen J, Fahrner J, Fatemi A, Harris J, Nowak C, Stevens C, Grand K, Au M, Graham J, Sanchez‐Lara P, Del Campo M, Jones M, Abdul‐Rahman O, Alkuraya F, Bassetti J, Bergstrom K, Bhoj E, Dugan S, Kaplan J, Derar N, Gripp K, Hauser N, Innes A, Keena B, Kodra N, Miller R, Nelson B, Nowaczyk M, Rahbeeni Z, Ben‐Shachar S, Shieh J, Slavotinek A, Sobering A, Abbott M, Allain D, Amlie‐Wolf L, Au P, Bedoukian E, Beek G, Barry J, Berg J, Bernstein J, Cytrynbaum C, Chung B, Donoghue S, Dorrani N, Eaton A, Flores‐Daboub J, Dubbs H, Felix C, Fong C, Fung J, Gangaram B, Goldstein A, Greenberg R, Ha T, Hersh J, Izumi K, Kallish S, Kravets E, Kwok P, Jobling R, Johnson A, Kushner J, Lee B, Levin B, Lindstrom K, Manickam K, Mardach R, McCormick E, McLeod D, Mentch F, Minks K, Muraresku C, Nelson S, Porazzi P, Pichurin P, Powell‐Hamilton N, Powis Z, Ritter A, Rogers C, Rohena L, Ronspies C, Schroeder A, Stark Z, Starr L, Stoler J, Suwannarat P, Velinov M, Weksberg R, Wilnai Y, Zadeh N, Zand D, Falk M, Hakonarson H, Zackai E, Quintero‐Rivera F. Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann‐Steiner syndrome. American Journal Of Medical Genetics Part A 2021, 185: 1649-1665. PMID: 33783954, PMCID: PMC8631250, DOI: 10.1002/ajmg.a.62124.Peer-Reviewed Original ResearchConceptsIntellectual disabilityWiedemann-Steiner syndromeGenotype-phenotype correlationDevelopmental trajectoriesDevelopmental milestonesClinician's differential diagnosisAssociated with loss of functionLong-term outcomesDiverse cohortAutosomal dominant disorderEthnically diverse cohortAssociated with lossDevelopmental delayDisabilityMedian ageClinical featuresMonoallelic variantsShort statureDifferential diagnosisPhenotypic spectrumHypertrichosis cubitiIndividualsMedical comorbiditiesDominant disorderFeeding difficulties
2018
De novo truncating variants in WHSC1 recapitulate the Wolf–Hirschhorn (4p16.3 microdeletion) syndrome phenotype
Derar N, Al-Hassnan Z, Al-Owain M, Monies D, Abouelhoda M, Meyer B, Moghrabi N, Alkuraya F. De novo truncating variants in WHSC1 recapitulate the Wolf–Hirschhorn (4p16.3 microdeletion) syndrome phenotype. Genetics In Medicine 2018, 21: 185-188. PMID: 29892088, DOI: 10.1038/s41436-018-0014-8.Peer-Reviewed Original ResearchConceptsDe novo truncating variantsHaploinsufficiency of multiple genesSingle-gene levelMicrodeletion syndromeDisease genesGenomic disordersExome sequencingMultiple genesSingle-geneWHSC1Syndrome phenotypeCore phenotypePhenotypePhenotypic expressionLociWolf-HirschhornGenesPhenotypic componentsMicrodeletionHaploinsufficiencyVariantsMilder variantsHemizygosityConclusionOur studySequence
2016
Characterizing the morbid genome of ciliopathies
Shaheen R, Szymanska K, Basu B, Patel N, Ewida N, Faqeih E, Al Hashem A, Derar N, Alsharif H, Aldahmesh M, Alazami A, Hashem M, Ibrahim N, Abdulwahab F, Sonbul R, Alkuraya H, Alnemer M, Al Tala S, Al-Husain M, Morsy H, Seidahmed M, Meriki N, Al-Owain M, AlShahwan S, Tabarki B, Salih M, Ciliopathy WorkingGroup, Faquih T, El-Kalioby M, Ueffing M, Boldt K, Logan C, Parry D, Al Tassan N, Monies D, Megarbane A, Abouelhoda M, Halees A, Johnson C, Alkuraya F. Characterizing the morbid genome of ciliopathies. Genome Biology 2016, 17: 242. PMID: 27894351, PMCID: PMC5126998, DOI: 10.1186/s13059-016-1099-5.Peer-Reviewed Original ResearchConceptsCombined carrier frequencyLoss of function mutationsGenetically heterogeneous conditionCiliopathy phenotypesGenomic analysisGenomic approachesCiliary signalingCiliopathy genesNovel allelesFounder mutationMendelian inheritanceCiliopathy spectrumMeckel-Gruber syndromeBardet-Biedl syndromePrimary ciliaThiol isomerasesFunction mutationsMolecular basisCiliopathiesMutation loadMutationsMeckel-GruberAffected individualsGenesVariable expression