0000000000395136

AUTHOR

Eva Lausberg

showing 2 related works from this author

C2orf69 mutations disrupt mitochondrial function and cause a multisystem human disorder with recurring autoinflammation

2021

BACKGROUND. Deciphering the function of the many genes previously classified as uncharacterized open reading frame (ORF) would complete our understanding of a cell’s function and its pathophysiology. METHODS. Whole-exome sequencing, yeast 2-hybrid and transcriptome analyses, and molecular characterization were performed in this study to uncover the function of the C2orf69 gene. RESULTS. We identified loss-of-function mutations in the uncharacterized C2orf69 gene in 8 individuals with brain abnormalities involving hypomyelination and microcephaly, liver dysfunction, and recurrent autoinflammation. C2orf69 contains an N-terminal signal peptide that is required and sufficient for mitochondrial…

0301 basic medicineMicrocephalyRespiratory chainBiologyMitochondrionCell LineMitochondrial ProteinsTranscriptomeMiceOpen Reading Frames03 medical and health sciencesAll institutes and research themes of the Radboud University Medical Center0302 clinical medicineLoss of Function MutationGlycogen branching enzymemedicineAnimalsHumansGeneMice KnockoutGeneticsMetabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]Glycogen Debranching Enzyme SystemGeneral Medicinemedicine.diseaseMitochondriaOpen reading frameRenal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]030104 developmental biology030220 oncology & carcinogenesisMicrocephalybiology.proteinClinical MedicineSignal transductionGlycogenJournal of Clinical Investigation
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A human multisystem disorder with autoinflammation, leukoencephalopathy and hepatopathy is caused by mutations in C2orf69

2021

AbstractBackgroundDeciphering the function of the many genes previously classified as uncharacterized “open reading frame” (orf) completes our understanding of cell function and its pathophysiology.MethodsWhole-exome sequencing, yeast 2-hybrid and transcriptome analyses together with molecular characterization are used here to uncover the function of the C2orf69 gene.ResultsWe identify loss-of-function mutations in the uncharacterized C2orf69 gene in eight individuals with brain abnormalities involving hypomyelination and microcephaly, liver dysfunction and recurrent autoinflammation. C2orf69 contains an N-terminal signal peptide that is required and sufficient for mitochondrial localizatio…

Signal peptideGeneticsTranscriptomeMicrocephalyOpen reading framebiologymedicineRespiratory chainGlycogen branching enzymebiology.proteinSignal transductionmedicine.diseaseGene
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