Novel Mutation Identified in Infantile Spasm Syndrome Patient

Overview

Journal Hum Genome Var

Date 2020 Apr 8

PMID 32257294

Citations 1

Authors

Yohei Takeshita

Tatsuyuki Ohto

Takashi Enokizono

Mai Tanaka

Hisato Suzuki

Hiroko Fukushima

Tomoko Uehara

Toshiki Takenouchi

Kenjiro Kosaki

Hidetoshi Takada

Affiliations

Soon will be listed here.

Abstract

We report a 7-year-old boy with infantile spasms caused by a novel mutation in the () gene. He showed infantile spasms and hypsarrhythmia on electroencephalogram from early infancy. Brain MRI did not reveal severe malformation of the brain except mild hypoplasia of the corpus callosum. Two-fold adrenocorticotropic hormone (ACTH) therapy failed to control the seizures, and ketogenic diet therapy and multi-antiepileptic drug therapy were required as he showed intractable daily tonic-clonic seizures. Exome sequencing identified a hemizygous mutation in the gene, NG_008281.1(ARX_v001):c.1448 + 1 G > A, chrX: 25025227 C > T (GRCh37). To our knowledge, this mutation has not been reported previously.

Citing Articles

Genotype-driven therapeutics in DEE and metabolic epilepsy: navigating treatment efficacy and drug resistance.

Nguyen Y, Vu B, Nguyen D, Quach N, Bui L, Hong J Sci Rep. 2024; 14(1):21606.

PMID: 39285222 PMC: 11405402. DOI: 10.1038/s41598-024-72683-7.

References

Takenouchi T, Yamaguchi Y, Tanikawa A, Kosaki R, Okano H, Kosaki K . Novel overgrowth syndrome phenotype due to recurrent de novo PDGFRB mutation. J Pediatr. 2014; 166(2):483-6. DOI: 10.1016/j.jpeds.2014.10.015. View

Gage B, Asadi A, Baker R, Webber T, Wang R, Itoh M . The Role of ARX in Human Pancreatic Endocrine Specification. PLoS One. 2015; 10(12):e0144100. PMC: 4669132. DOI: 10.1371/journal.pone.0144100. View

Nasrallah I, Minarcik J, Golden J . A polyalanine tract expansion in Arx forms intranuclear inclusions and results in increased cell death. J Cell Biol. 2004; 167(3):411-6. PMC: 2172475. DOI: 10.1083/jcb.200408091. View

Dubos A, Meziane H, Iacono G, Curie A, Riet F, Martin C . A new mouse model of ARX dup24 recapitulates the patients' behavioral and fine motor alterations. Hum Mol Genet. 2018; 27(12):2138-2153. PMC: 5985730. DOI: 10.1093/hmg/ddy122. View

Kitamura K, Yanazawa M, Sugiyama N, Miura H, Iizuka-Kogo A, Kusaka M . Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. Nat Genet. 2002; 32(3):359-69. DOI: 10.1038/ng1009. View

Bienvenu T, Poirier K, Friocourt G, Bahi N, Beaumont D, Fauchereau F . ARX, a novel Prd-class-homeobox gene highly expressed in the telencephalon, is mutated in X-linked mental retardation. Hum Mol Genet. 2002; 11(8):981-91. DOI: 10.1093/hmg/11.8.981. View

Stromme P, Mangelsdorf M, Shaw M, Lower K, Lewis S, Bruyere H . Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy. Nat Genet. 2002; 30(4):441-5. DOI: 10.1038/ng862. View

Kato M, Das S, Petras K, Kitamura K, Morohashi K, Abuelo D . Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation. Hum Mutat. 2004; 23(2):147-159. DOI: 10.1002/humu.10310. View

Ohira R, Zhang Y, Guo W, Dipple K, Shih S, Doerr J . Human ARX gene: genomic characterization and expression. Mol Genet Metab. 2002; 77(1-2):179-88. DOI: 10.1016/s1096-7192(02)00126-9. View

10.

Friocourt G, Parnavelas J . Mutations in ARX Result in Several Defects Involving GABAergic Neurons. Front Cell Neurosci. 2010; 4:4. PMC: 2841486. DOI: 10.3389/fncel.2010.00004. View

11.

Kato M, Koyama N, Ohta M, Miura K, Hayasaka K . Frameshift mutations of the ARX gene in familial Ohtahara syndrome. Epilepsia. 2010; 51(9):1679-84. DOI: 10.1111/j.1528-1167.2010.02559.x. View

12.

Shoubridge C, Jackson M, Grinton B, Berkovic S, Scheffer I, Huskins S . Splice variant in ARX leading to loss of C-terminal region in a boy with intellectual disability and infantile onset developmental and epileptic encephalopathy. Am J Med Genet A. 2019; 179(8):1483-1490. DOI: 10.1002/ajmg.a.61216. View

13.

Olivetti P, Noebels J . Interneuron, interrupted: molecular pathogenesis of ARX mutations and X-linked infantile spasms. Curr Opin Neurobiol. 2012; 22(5):859-65. PMC: 3437236. DOI: 10.1016/j.conb.2012.04.006. View

14.

Kato M . Genotype-phenotype correlation in neuronal migration disorders and cortical dysplasias. Front Neurosci. 2015; 9:181. PMC: 4439546. DOI: 10.3389/fnins.2015.00181. View