Clinical characteristics and mutation analysis of five cases of epilepsy with <i>ADGRV1</i> gene mutation_Journal of Epilepsy

Authors：

MA Mengyu ^1,2 , QIAO Baojun ² , LIU Yidan ^1,2 , SUN Ying ³ , WU Xingrao ² , ZHANG Yanke ² , LI Qiubo ⁴ , ZHANG Junchen ⁵ ,  KONG Qingxia ^2,6

1. Cheeloo College of Medicine, Shandong University, Jinan 250012, China;
2. Department of Neurology, Affiliated Hospital of Jining Medical University, Jining 272000, China;
3. Intensive Care Unit, North China Medical Feng Feng General Hospital, Handan 056200, China;
4. Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining 272000, China;
5. Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining 272000, China;
6. Institute of Epilepsy, Jining Medical University, Jining 272000, China;

Corresponding author：

KONG Qingxia, Email: kxdqy8@sohu.com

Keywords：

Epilepsy; Gene Mutation; ADGRV1

DOI：

10.7507/2096-0247.20210035

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Objective To analyze the clinical and genetic characteristics of ADGRV1 gene mutation epilepsy.Methods A retrospective collection of 26 patients with epilepsy diagnosed and related gene sequencing was performed in the Affiliated Hospital of Jining Medical College from January 2018 to December 2018. Five epilepsy patients with ADGRV1 mutations were screened out, and their clinical characteristics and gene mutation characteristics were summarized.Results A total of 5 epilepsy patients with ADGRV1 mutation were collected, including 1 male and 4 females, with an average age of (7±5.83) years. Three patients had a family history of epilepsy, and the father of the other two patients had a history of febrile seizures. 2 cases showed generalized tonic-clonic seizures, and 3 cases showed partial seizures followed by generalized seizures. The results of genetic testing revealed 7 mutation sites in the ADGRV1 gene, of which one missense mutation site c.2039A>G has been reported in the literature. Two of the 5 patients underwent epilepsy surgery, and they were still treated with multiple anti-epileptic drugs for a long time after the operation, and the other 3 patients were treated with anti-epileptic drugs for a long time. At present, 4 out of 5 patients had seizures still not under effective control, and 1 case did not relapse after being followed up for nearly 1 year.Conclusion The clinical features of epilepsy caused by ADGRV1 gene mutation are early onset, mainly manifested as general tonic-clonic seizures or partial seizures secondary to generalized seizures, accompanied by disturbance of consciousness during seizures. The combined treatment of anti-epileptic drugs and postoperative anti-epileptic drugs is less effective. Genetic testing can guide genetic counseling and assisted diagnosis.

Citation： MA Mengyu, QIAO Baojun, LIU Yidan, SUN Ying, WU Xingrao, ZHANG Yanke, LI Qiubo, ZHANG Junchen, KONG Qingxia. Clinical characteristics and mutation analysis of five cases of epilepsy with ADGRV1 gene mutation. Journal of Epilepsy, 2021, 7(3): 228-233. doi: 10.7507/2096-0247.20210035 Copy

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10.	Klein BD, Fu Y-H, Ptacek LJ, et al. Auditory deficits associated with the frings mgr1 (mass1) mutation in mice. Dev Neurosci, 2005, 27(5): 321-332.
11.	Johnson KR, Zheng QY, Weston MD, et al. The Mass1frings mutation underlies early onset hearing impairment in BUB/BnJ mice, a model for the auditory pathology of Usher syndrome IIC. Genomics, 2005, 85(5): 582-590.
12.	Yagi H, Takamura Y, Yoneda T, et al. Vlgr1 knockout mice show audiogenic seizure susceptibility. J Neurochem, 2005, 92(1): 191-202.

1. Sans N, Vissel B, Petralia R, et al. A novel gene causing a mendelian audiogenic mouse epilepsy. Neuron, 2001, 31(4): 537-544.
2. McMillan DR, White PC. Loss of the transmembrane and cytoplasmic domains of the very large G-protein-coupled receptor-1 (VLGR1 or Mass1) causes audiogenic seizures in mice. Mol Cell Neurosci, 2004, 26(2): 322-329.
3. Nakayama J, Fu Y-H, Clark AM, et al. A nonsense mutation of theMASS1 gene in a family with febrile and afebrile seizures. Annals of Neurology, 2002, 52(5): 654-657.
4. Weston MD, Luijendijk MW, Humphrey KD, et al. Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II. Am J Hum Genet, 2004, 74(2): 357-366.
5. Myers KA, Nasioulas S, Boys A, et al. ADGRV1 is implicated in myoclonic epilepsy. Epilepsia, 2018, 59(2): 381-388.
6. Robinson R, Gardiner M. Molecular basis of Mendelian idiopathic epilepsies. Annals of Medicine, 2009, 36(2): 89-97.
7. Shin D, Lin ST, Fu YH, et al. Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via Galphas/Galphaq-mediated protein kinases A/C. Proc Natl Acad Sci U SA, 2013, 110(47): 19101-19106.
8. Yan W, Long P, Chen T, et al. A natural occurring mouse model with Adgrv1 mutation of usher syndrome 2C and characterization of its recombinant inbred strains. Cell Physiol Biochem, 2018, 47(5): 1883-1897.
9. Scheel H, Tomiuk SKH. A common protein interaction domain links two recently identified epilepsy genes. Hum Mol Genet, 2002, 11(15): 1757-1762.
10. Klein BD, Fu Y-H, Ptacek LJ, et al. Auditory deficits associated with the frings mgr1 (mass1) mutation in mice. Dev Neurosci, 2005, 27(5): 321-332.
11. Johnson KR, Zheng QY, Weston MD, et al. The Mass1frings mutation underlies early onset hearing impairment in BUB/BnJ mice, a model for the auditory pathology of Usher syndrome IIC. Genomics, 2005, 85(5): 582-590.
12. Yagi H, Takamura Y, Yoneda T, et al. Vlgr1 knockout mice show audiogenic seizure susceptibility. J Neurochem, 2005, 92(1): 191-202.

Journal of Epilepsy

Clinical characteristics and mutation analysis of five cases of epilepsy with ADGRV1 gene mutation

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