Screening of the Duplication 24 Pb of ARX Gene in Moroccan Patients with X-linked Intellectual Disability

Overview

Journal BMC Res Notes

Publisher Biomed Central

Specialties Biology
General Medicine

Date 2021 Mar 24

PMID 33757564

Citations 1

Authors

Yousra Benmakhlouf

Renaud Touraine

Ines Harzallah

Zeineb Zian

Kaoutar Ben Makhlouf

Amina Barakat

Naima Ghailani Nourouti

Mohcine Bennani Mechita

Affiliations

Soon will be listed here.

Abstract

Objective: Intellectual Disability (ID) represents a neuropsychiatric disorder, which its etiopathogenesis remains insufficiently understood. Mutations in the Aristaless Related Homeobox gene (ARX) have been identified to cause syndromic and nonsyndromic (NS-ID). The most recurrent mutation of this gene is a duplication of 24pb, c.428-451dup. Epidemiological and genetic studies about ID in the Moroccan population remain very scarce, and none study is carried out on the ARX gene. This work aimed to study c.428-451dup (24 bp) mutation in the exon 2 of the ARX gene in 118 males' Moroccan patients with milder NS-ID to evaluate if the gene screening is a good tool for identifying NS-ID.

Results: Our mutational analysis did not show any dup(24pb) in our patients. This is because based on findings from previous studies that found ARX mutations in 70% of families with NS-ID, and in most cases, 1.5-6.1% of individuals with NS-ID have this duplication. Since 1/118 = 0.0084 (0.84%) is not much different from 1.5%, then it is reasonable that this could a sample size artifact. A complete screening of the entire ARX gene, including the five exons, should be fulfilled. Further investigations are required to confirm these results.

Citing Articles

Sociodemographic Factors and Consanguinity in Intellectual Disability: A Pilot Study.

Benmakhlouf Y, Laghmich A, Ben Makhlouf K, Barakat A, Ghailani Nourouti N, Bennani Mechita M Innov Clin Neurosci. 2025; 21(10):9-14.

PMID: 39790896 PMC: 11709441.

Phenotypes of a female patient with novel de novo frameshift ARX variant identified by whole-exome sequencing: a case report.

Iskandar K, Herini E, Triono A, Hadiyanto M, Nugrahanto A, Gunadi Ann Med Surg (Lond). 2023; 85(2):236-241.

PMID: 36845779 PMC: 9949785. DOI: 10.1097/MS9.0000000000000197.

References

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

Ishibashi M, Manning E, Shoubridge C, Krecsmarik M, Hawkins T, Giacomotto J . Copy number variants in patients with intellectual disability affect the regulation of ARX transcription factor gene. Hum Genet. 2015; 134(11-12):1163-82. DOI: 10.1007/s00439-015-1594-x. View

Poirier K, Eisermann M, Caubel I, Kaminska A, Peudonnier S, Boddaert N . Combination of infantile spasms, non-epileptic seizures and complex movement disorder: a new case of ARX-related epilepsy. Epilepsy Res. 2008; 80(2-3):224-8. DOI: 10.1016/j.eplepsyres.2008.03.019. View

Suri M . The phenotypic spectrum of ARX mutations. Dev Med Child Neurol. 2005; 47(2):133-7. DOI: 10.1017/s001216220500023x. View

Depositario-Cabacar D, Zelleke T . Treatment of epilepsy in children with developmental disabilities. Dev Disabil Res Rev. 2010; 16(3):239-47. DOI: 10.1002/ddrr.116. View

Lee K, Mattiske T, Kitamura K, Gecz J, Shoubridge C . Reduced polyalanine-expanded Arx mutant protein in developing mouse subpallium alters Lmo1 transcriptional regulation. Hum Mol Genet. 2013; 23(4):1084-94. DOI: 10.1093/hmg/ddt503. View

Kato M, Saitoh S, Kamei A, Shiraishi H, Ueda Y, Akasaka M . A longer polyalanine expansion mutation in the ARX gene causes early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome). Am J Hum Genet. 2007; 81(2):361-6. PMC: 1950814. DOI: 10.1086/518903. 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

Abedini S, Kahrizi K, Behjati F, Banihashemi S, Ghasemi Firoozabadi S, Najmabadi H . Mutational screening of ARX gene in Iranian families with X-linked intellectual disability. Arch Iran Med. 2012; 15(6):361-5. DOI: 012156/AIM.009. View

10.

de Brouwer A, Yntema H, Kleefstra T, Lugtenberg D, Oudakker A, de Vries B . Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium. Hum Mutat. 2007; 28(2):207-8. DOI: 10.1002/humu.9482. View

11.

Benmakhlouf Y, Zian Z, Ben Makhlouf K, Ghailani Nourouti N, Barakat A, Bennani Mechita M . Intellectual Disability in Morocco: A Pilot Study. Innov Clin Neurosci. 2021; 17(10-12):9-13. PMC: 7819583. View

12.

Partington M, Turner G, Boyle J, Gecz J . Three new families with X-linked mental retardation caused by the 428-451dup(24bp) mutation in ARX. Clin Genet. 2004; 66(1):39-45. DOI: 10.1111/j.0009-9163.2004.00268.x. View

13.

Wohlrab G, Uyanik G, Gross C, Hehr U, Winkler J, Schmitt B . Familial West syndrome and dystonia caused by an Aristaless related homeobox gene mutation. Eur J Pediatr. 2005; 164(5):326-8. DOI: 10.1007/s00431-005-1622-2. View

14.

Rujirabanjerd S, Tongsippunyoo K, Sripo T, Limprasert P . Mutation screening of the Aristaless-related homeobox (ARX) gene in Thai pediatric patients with delayed development: first report from Thailand. Eur J Med Genet. 2007; 50(5):346-54. DOI: 10.1016/j.ejmg.2007.05.003. View

15.

Lee K, Ireland K, Bleeze M, Shoubridge C . ARX polyalanine expansion mutations lead to migration impediment in the rostral cortex coupled with a developmental deficit of calbindin-positive cortical GABAergic interneurons. Neuroscience. 2017; 357:220-231. DOI: 10.1016/j.neuroscience.2017.06.010. View

16.

Poirier K, Lacombe D, Gilbert-Dussardier B, Raynaud M, Desportes V, de Brouwer A . Screening of ARX in mental retardation families: Consequences for the strategy of molecular diagnosis. Neurogenetics. 2005; 7(1):39-46. DOI: 10.1007/s10048-005-0014-0. View

17.

Mattiske T, Tan M, Dearsley O, Cloosterman D, Hii C, Gecz J . Regulating transcriptional activity by phosphorylation: A new mechanism for the ARX homeodomain transcription factor. PLoS One. 2018; 13(11):e0206914. PMC: 6231642. DOI: 10.1371/journal.pone.0206914. View

18.

Fullston T, Finnis M, Hackett A, Hodgson B, Brueton L, Baynam G . Screening and cell-based assessment of mutations in the Aristaless-related homeobox (ARX) gene. Clin Genet. 2011; 80(6):510-22. DOI: 10.1111/j.1399-0004.2011.01685.x. View

19.

Guerrini R, Moro F, Kato M, Barkovich A, Shiihara T, McShane M . Expansion of the first PolyA tract of ARX causes infantile spasms and status dystonicus. Neurology. 2007; 69(5):427-33. DOI: 10.1212/01.wnl.0000266594.16202.c1. View

20.

Gronskov K, Hjalgrim H, Nielsen I, Brondum-Nielsen K . Screening of the ARX gene in 682 retarded males. Eur J Hum Genet. 2004; 12(9):701-5. DOI: 10.1038/sj.ejhg.5201222. View