Abstract
Gordon Holmes syndrome (GHS) is a rare disease characterized by hypogonadotropic hypogonadism (HH), progressive cognitive decline and variable movement disorders. Mutations in RNF216 have been found to be associated with GHS. Here, we identify a novel homozygous RNF216 p.E650X mutation causing GHS. The proband presented with onset dysarthria and developed cerebellar ataxia and cognitive impairment, with a history of azoospermia at the age of 28 years. Cerebellar atrophy and white matter lesions were found in the cerebral hemispheres and brainstem. Low gonadotropin serum levels were also observed. Whole-exome sequencing (WES) revealed a novel homozygous nonsense variant in RNF216, c.1948G>T; p.E650X. Our finding furthers the genetic knowledge of GHS and extends the ethnic distribution of RNF216 mutations.
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Acknowledgments
The authors thank the patient and their family for their cooperation in this study.
Funding
This study was supported by grants from the National Natural Science Foundation of China (grant number 91849126).
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Jin-Tai Yu, Mei Cui, and Qiang Dong contributed to the study conception and design. Collection and assembly of data were performed by Ke-Liang Chen, Gui-Xian Zhao, Lei Wei, Shi-Dong Chen, Yu-Yuang Huang, and Jian Sun. Data analysis and interpretation were performed by Ke-Liang Chen, He Wang, Lei Wei, Jin-Tai Yu and Mei Cui. The first draft of the manuscript was written by Ke-Liang Chen, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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This study was approved by the Ethics Committee of Huashan Hospital. The methods in this study were performed in accordance with the approved guidelines.
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Ke-Liang Chen and He Wang contributed equally to the manuscript.
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Chen, KL., Wang, H., Zhao, GX. et al. Whole-Exome Sequencing Identified a Novel Mutation in RNF216 in a Family with Gordon Holmes Syndrome. J Mol Neurosci 72, 691–694 (2022). https://doi.org/10.1007/s12031-021-01953-0
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DOI: https://doi.org/10.1007/s12031-021-01953-0