DataSheet1_A novel non-sense variant in the OFD1 gene caused Joubert syndrome.zip
Background: Joubert syndrome (JBS) is a rare neurodevelopmental disorder associated with progressive renal, liver, and retinal involvement that exhibits heterogeneity in both clinical manifestations and genetic etiology. Therefore, it is difficult to make a definite prenatal diagnosis.
Methods: Whole-exome sequencing and Sanger sequencing were performed to screen the causative gene variants in a suspected JBS family. RNA-seq and protein model prediction were performed to clarify the potential pathogenic mechanism. A more comprehensive review of previously reported cases with OFD1 variants is presented and may help to establish a genotype–phenotype.
Results: We identified a novel non-sense variant in the OFD1 gene, OFD1 (NM_003611.3): c.2848A>T (p.Lys950Ter). Sanger sequencing confirmed cosegregation among this family. RNA-seq confirmed that partial degradation of mutant transcripts, which was predicted to be caused by the non-sense-mediated mRNA decay (NMD) mechanism, may explain the reduction in the proportion of mutant transcripts. Protein structure prediction of the non-sense variant transcript revealed that this variant may lead to a change in the OFD1 protein structure.
Conclusion: The genetic variation spectrum of JBS10 caused by OFD1 was broadened. The novel variants further deepened our insight into the molecular mechanism of the disease.
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- Gene and Molecular Therapy
- Gene Expression (incl. Microarray and other genome-wide approaches)
- Genetics
- Genetically Modified Animals
- Livestock Cloning
- Developmental Genetics (incl. Sex Determination)
- Epigenetics (incl. Genome Methylation and Epigenomics)
- Biomarkers
- Genomics
- Genome Structure and Regulation
- Genetic Engineering