Analysis of the clinical phenotype and neurological developmental quotient in children with epilepsy and <i>GPR98</i> gene mutation_Journal of Epilepsy

Authors：

 ZHUOMuqing , WANGLingan ,  ZHAIQiongxiang , ZHANGYuxin , CHENZhihong , GUOYuxiong , CHENYishan , WANGChun

Department of Pediatrics, Guangdong General Hospital(Guangdong Academy of Medical Sciences), Guangzhou, 510080, China;

Corresponding author：

ZHAIQiongxiang, Email: zhaiqiongxiang@sina.com

Keywords：

GPR98 gene mutation; Epilepsy; Developmental quotient; Clinical phenotype

DOI：

10.7507/2096-0247.20150015

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Objective To study the relation between the clinical phenotype and neurological developmental quotient in children with epilepsy and GPR98 gene mutation. Methods Genomic DNA was extracted from peripheral blood lymphocytes of the probands and other available members in the epilepsy families.Clinical datas and screened for mutations by next-generation sequencing conbined target sequencing technology and PCR and direct DNA sequencing were collected.Then, the relations between the clinical phenotype and developmental quotient in children with epilepsy and GPR98 gene mutation was analyzed. Results Seven novel GPR98 gene mutations were found in seven probands in 65 families, including six heterozygote missense mutations (c.6083C <、c.1969A < C、c.17531C < T、c.9069G < C、c.6661G < A and c.18496A < C) and one nonsense mutation (c.14224G < T). One of their parents carried the same GPR98 gene mutation as the proband's. The initial symptom of six cases was afebrile seizures and one showed febrile seizure, in which the main type seizure was generalized seizure.Moreover, was were significant difference between children with epilepsy and GPR98 gene mutations and healthy children in developmental quotient test(P < 0.01). Conclusions The main type of seizures in children with epilepsy and GPR98 gene mutations is generalized seizure. Furthermore, GPR98 gene mutations may be associated with psychomotor retardation.

Citation： ZHUOMuqing, WANGLingan, ZHAIQiongxiang, ZHANGYuxin, CHENZhihong, GUOYuxiong, CHENYishan, WANGChun. Analysis of the clinical phenotype and neurological developmental quotient in children with epilepsy and GPR98 gene mutation. Journal of Epilepsy, 2015, 1(2): 106-111. doi: 10.7507/2096-0247.20150015 Copy

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1. Ngugi AK, Bottomley C, Fegan G, et al. Premature mortality in active convulsive epilepsy in rural Kenya:causes and associated factors. Neurology, 2014, 82(7):582-589.
2. 林庆, 刘晓燕, 秦炯.实用小儿癫痫病学.北京:北京科学技术出版社, 2004:47-51.
3. Hamann J, Aust G, Arac D, et al. International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors. Pharmacol Rev, 2015, 67(2):338-367.
4. Nakayama J, Fu YH, Clark AM, et al. A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizure. Ann Neurol, 2002, 52(5):654-657.
5. Weston MD, Luijendijk MW, Humphrey KD, et al. Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome typeⅡ. Am J Hum Genet, 2004, 74(2):357-366.
6. Nakayama J, Hamano K, Iwasaki N, et al. Significant evidence for linkage of febrile seizures to chromosome 5q14-q15. Hum Mol Genet, 2000, 9(1):87-91.
7. Mcmillan DR, Kayes-Wandover KM, Richardson JA, et al. Very large G protein-coupled receptor-1, the largest known cell surface protein, is highly expressed in the developing central nervous system. J Biol Chem, 2002, 277(1):785-792.
8. Deprez L, Claes LR, Claeys KG, et al. Genome-wide linkage of febrile seizures and epilepsy to the FEB4 locus at 5q14.3-q23.1 and no MASS1 mutation. Hum Genet, 2006, 118(5):618-625.
9. Yagi H, Noguchi Y, Kitamura K, et al. Deficiency of Vlgr1 resulted in deafness and susceptibility to audiogenic seizures while the degree of hearing impairment was not correlated with seizure severity in C57BL/6-and 129-backcrossed lines of Vlgr1 knockout mice. Neurosci Lett, 2009, 461(2):190-195.
10. Yagi H, Takamura Y, Yoneda T, et al. Vlgr1 knockout mice show audiogenic seizure susceptibility. J Neurochem, 2005(92):191-202.
11. Garcia-Garcia G, Besnard T, Baux D, et al. The contribution of GPR98 and DFNB31 genes to a Spanish Usher syndrome type 2 cohort. Mol Vis, 2013, 9(2):367-373.
12. 林广杰, 李文, 魏国强, 等. Usher综合征.中国医药指南, 2012(33):448-449.
13. Pieke-Dahl S, Moller CG, Kelley PM, et al. Genetic heterogeneity of Usher syndrome typeⅡ:localisation to chromosome 5q. J Med Genet, 2000, 37(4):256-262.

Journal of Epilepsy

Analysis of the clinical phenotype and neurological developmental quotient in children with epilepsy and GPR98 gene mutation

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