2023
PRSS8, encoding prostasin, is mutated in patients with autosomal recessive ichthyosis
Shamseldin H, Derar N, Alzaidan H, AlHathal N, Alfalah A, Abdulwahab F, Alzaid T, Alkeraye S, Alobaida S, Alkuraya F. PRSS8, encoding prostasin, is mutated in patients with autosomal recessive ichthyosis. Human Genetics 2023, 142: 477-482. PMID: 36715754, DOI: 10.1007/s00439-023-02527-3.Peer-Reviewed Original ResearchConceptsCanonical splice sitesAssociated with reduced abundanceDeleterious variantsLinkage locusSplice siteNormal transcriptionMissense variantsExome sequencingConsanguineous familyAutosomal recessive ichthyosisRecessive ichthyosisPRSS8VariantsKnockout miceCongenital ichthyosisExomeProstasinSkin histopathologyHuman patientsMissenseScaly skinLociIchthyosisTranscriptionFamily
2020
Analysis of transcript-deleterious variants in Mendelian disorders: implications for RNA-based diagnostics
Maddirevula S, Kuwahara H, Ewida N, Shamseldin H, Patel N, Alzahrani F, AlSheddi T, AlObeid E, Alenazi M, Alsaif H, Alqahtani M, AlAli M, Al Ali H, Helaby R, Ibrahim N, Abdulwahab F, Hashem M, Hanna N, Monies D, Derar N, Alsagheir A, Alhashem A, Alsaleem B, Alhebbi H, Wali S, Umarov R, Gao X, Alkuraya F. Analysis of transcript-deleterious variants in Mendelian disorders: implications for RNA-based diagnostics. Genome Biology 2020, 21: 145. PMID: 32552793, PMCID: PMC7298854, DOI: 10.1186/s13059-020-02053-9.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingMendelian disordersMendelian diseasesRNA-seqDiagnosis of Mendelian diseasesRNA analysisNon-coding variantsSuspected Mendelian diseasesSuspected Mendelian disordersBlood-derived RNARNA-based diagnosticsWhole-transcriptome sequencingIn silico predictionGenome sequenceRT-PCRMendelian phenotypesTranscriptome sequencingRNA sourceResults of RT-PCRModulate penetranceRNASequenceConclusionsOur resultsVariantsGenome
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