Clinical Features and Mutation Analysis of Gordon Holmes Syndrome Associated with <i>RNF216</i> Gene Mutation and a Literature Review

CHEN Meiping; YANG Hongbo; PAN Hui; FENG Feng; ZHU Yicheng; ZHU Huijuan

doi:10.12376/j.issn.2097-0501.2023.03.004

Journal of Rare Diseases > 2023 > 2(3): 337-345. > DOI: 10.12376/j.issn.2097-0501.2023.03.004

CHEN Meiping, YANG Hongbo, PAN Hui, FENG Feng, ZHU Yicheng, ZHU Huijuan. Clinical Features and Mutation Analysis of Gordon Holmes Syndrome Associated with RNF216 Gene Mutation and a Literature Review[J]. Journal of Rare Diseases, 2023, 2(3): 337-345. DOI: 10.12376/j.issn.2097-0501.2023.03.004

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Clinical Features and Mutation Analysis of Gordon Holmes Syndrome Associated with RNF216 Gene Mutation and a Literature Review

1.
Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
2.
Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
3.
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

Funds:

Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences 2021-I2M-1-003

More Information

Corresponding author:
ZHU Huijuan, E-mail: shengxin2004@163.com
Received Date: June 09, 2023
Accepted Date: June 24, 2023

Graphical Abstract

Abstract

Abstract

Objective
To summarize the clinical characteristics and RNF216 gene mutation of a patient with Gordon Holmes syndrome (GHS), and to improve the understanding of the genetic and clinica characteristics of this disease through literature review.
Methods
We collected the clinical data of the patient with GHS, extracted the DNA from 2 mL peripheral venous blood of the patient and his parents for whole exome gene detection, and then we analyzed the clinical and genetic characteristics of all previously reported patients with RNF216 gene mutation.
Results
The young male patient was short in stature at sixyearsold and was diagnosed growth hormone deficiency.He had no secondary sexual characteristics by the age of 15 and was diagnosed hypogonadal hypogonadism.After the age of 22, he gradually developed abnormal gait and had progressive decline in speech, motor, and cognitive functions.Whole exome sequencing revealed a homozygous, nonsense mutation c.1549C>T (p.R517*) in the RNF216 gene.His parents were consanguineous and were heterozygous carriers of the mutations with phenotypic normality.Combined with literature review and this case report results showed that a total of 21 patients of the disease in the world and among them 15 had pathogenic variants of RNF216 gene mutation.7 of the 15 had truncated mutations, 5 had missense mutations, and 1 synonym mutation, 1 splice mutation, and 1 deletion mutation respectively.RNF216 gene mutation can be seen in neurodegenerative diseases with multiple overlapping symptoms of GHS, Huntington-like disease, and 4H syndrome.The main clinical manifestations are hypogonadotropic hypogonadism and early-onset progressive neurological dysfunction in adolescence or early adulthood.The median age of onset of neurological symptoms is 28 years old, featuring cerebellar ataxia, dysarthria, and cognitive impairment, as well as imaging manifestations of extensive white matter lesions and cerebellar atrophy.
Conclusions
The mutation of RNF216 gene can cause GHS.Genetic testing is helpful to the diagnosis and treatment of rare diseases.
- RNF216 gene,
- Gordon Holmes syndrome,
- hypogonadotropic hypogonadism,
- cerebellar ataxia,
- neurodegenerative diseases

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References (19)

References

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Clinical Features and Mutation Analysis of Gordon Holmes Syndrome Associated with RNF216 Gene Mutation and a Literature Review