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A novel homozygous missense mutation in the FASTKD2 gene leads to Lennox-Gastaut syndrome


FASTKD2 encodes an RNA-binding protein, which is a key post-transcriptional regulator of mitochondrial gene expression. Mutations in FASTKD2 have recently been found in mitochondrial encephalomyopathy, which is characterized by a deficiency in mitochondrial function. To date, seven patients have been reported. Six patients were identified with nonsense or frameshift mutations in the FASTKD2 gene, and only one patient harbored a missense mutation and a nonsense mutation. Here, we identified a novel FASTKD2 homozygous mutation, c.911 T > C, in a patient diagnosed with Lennox-Gastaut syndrome. We observed that the expression of FASTKD2 and the levels of mitochondrial 16 S rRNA were lower in the patient than in the unaffected controls. In conclusion, the missense mutation c.911 T > C caused loss of function in FASTKD2, which was associated with a new phenotype, Lennox-Gastaut syndrome.

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We thank the patients and their families for their participation in the study. We would like to thank Editage ( for the English language editing.

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TW drafted the manuscript and performed the experiments. LM and FY performed patient clinical management and analyzed the clinical data. CC analyzed the EEG data. JP supervised the work and designed of the research.

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Correspondence to Jing Peng.

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The authors declare no competing interests.

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This study was approved by the Ethics Committee of Xiangya Hospital of Central South University, China (Human study/protocol #201605585).

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Wu, T., Mao, L., Chen, C. et al. A novel homozygous missense mutation in the FASTKD2 gene leads to Lennox-Gastaut syndrome. J Hum Genet (2022).

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