AUTHOR=Li Chen , Wang Xingwang , Li Fake , Ding Hongke , Liu Ling , Xiong Ying , Yang Chaoxiang , Zhang Yan , Wu Jing , Yin Aihua
TITLE=A novel non-sense variant in the OFD1 gene caused Joubert syndrome
JOURNAL=Frontiers in Genetics
VOLUME=13
YEAR=2023
URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.1064762
DOI=10.3389/fgene.2022.1064762
ISSN=1664-8021
ABSTRACT=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.