Screening and cell-based assessment of mutations in the Aristaless-related homeobox (ARX) gene

Clinical Genetics

Volumn 80, Issue 6, 2011, Pages 510-522

  Fullston, T ^a,b   Finnis, M ^a   Hackett, A ^c   Hodgson, B ^a   Brueton, L ^d   Baynam, G ^e,f   Norman, A ^d   Reish, O ^g   Shoubridge, C ^a,b   Gecz, J ^a,b  

^a WOMEN S AND CHILDREN S HOSPITAL   (Australia)

^b UNIVERSITY OF ADELAIDE   (Australia)

^c Genetics of Learning Disability   (Australia)

^d BIRMINGHAM WOMEN S HOSPITAL   (United Kingdom)

^e Genetic Services of Western Australia   (Australia)

^f UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^g ASSAF HAROFEH MEDICAL CENTER   (Israel)

Author keywords

ARX; Intellectual disability; Mutation; Protein mislocalization; Screening; XLMR

Indexed keywords

ALANINE DERIVATIVE; DNA; HOMEODOMAIN PROTEIN; POLYALANINE 1; POLYALANINE 2; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR ARX; UNCLASSIFIED DRUG;

ARTICLE; CELLULAR DISTRIBUTION; CHILD; DENATURING HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; DISEASE SEVERITY; DNA SCREENING; FAMILY STUDY; FEMALE; GENE DUPLICATION; GENE MUTATION; GENETIC IDENTIFICATION; GENETIC VARIABILITY; GENOTYPE; HUMAN; INTELLECTUAL IMPAIRMENT; MAJOR CLINICAL STUDY; MALE; OPEN READING FRAME; PHENOTYPE; POINT MUTATION; PRESCHOOL CHILD; PRIORITY JOURNAL; PROTEIN FUNCTION; SCHOOL CHILD; SINGLE STRAND CONFORMATION POLYMORPHISM;

AUTISTIC DISORDER; BASE SEQUENCE; CHILD; CHILD, PRESCHOOL; CHROMOSOME DUPLICATION; COHORT STUDIES; CONSERVED SEQUENCE; DEVELOPMENTAL DISABILITIES; FEMALE; GENETIC ASSOCIATION STUDIES; GENETIC TESTING; HEK293 CELLS; HOMEODOMAIN PROTEINS; HUMANS; INFANT; MALE; MUTATION; MUTATION RATE; PEDIGREE; POLYMORPHISM, SINGLE-STRANDED CONFORMATIONAL; TRANSCRIPTION FACTORS;

EID: 80054890040     PISSN: 00099163     EISSN: 13990004     Source Type: Journal    
DOI: 10.1111/j.1399-0004.2011.01685.x     Document Type: Article

References (43)

1. Strømme P, Mangelsdorf ME, Shaw MA et al. Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy. Nat Genet 2002: 30: 441-445.
2. Bienvenu T, Poirier K, Friocourt G et al. ARX, a novel Prd-class-homeobox gene highly expressed in the telencephalon, is mutated in X-linked mental retardation. Hum Mol Genet 2002: 11: 981-991.
3. Kitamura K, Yanazawa M, Sugiyama N et al. 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: 359-369.
4. Colasante G, Sessa A, Crispi S et al. Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity. Dev Biol 2009: 334: 59-71.
5. Collombat P, Hecksher-Sørensen J, Broccoli V et al. The simultaneous loss of Arx and Pax4 genes promotes a somatostatin-producing cell fate specification at the expense of the alpha- and beta-cell lineages in the mouse endocrine pancreas. Development 2005: 132: 2969-2980.
6. McKenzie O, Ponte I, Mangelsdorf M et al. Aristaless-related homeobox gene, the gene responsible for West syndrome and related disorders, is a Groucho/transducin-like enhancer of split dependent transcriptional repressor. Neuroscience 2007: 146: 236-247.
7. Shoubridge C, Fullston T, Gécz J. 'ARX spectrum disorders'; making inroads in to the molecular pathology. Hum Mutat 2010: 31: 889-900.
8. Gécz J, Cloosterman D, Partington M. ARX: a gene for all seasons. Curr Opin Genet Dev 2006: 16: 308-316.
9. Kato M, Das S, Petras K et al. Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation. Hum Mutat 2004: 23: 147-159.
10. Marsh E, Fulp C, Gomez E et al. Targeted loss of Arx results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females. Brain 2009: 132: 1563-1576.
11. Turner G, Partington M, Kerr B, Mangelsdorf M, Gecz J. Variable expression of mental retardation, autism, seizures, and dystonic hand movements in two families with an identical ARX gene mutation. Am J Med Genet 2002: 112: 405-411.
12. Gestinari-Duarte RDS, Santos-Rebouças CB, Boy RT, Pimentel MM. ARX mutation c.428-451dup (24bp) in a Brazilian family with X-linked mental retardation. Eur J Med Genet 2006: 49: 269-275.
13. Szczaluba K, Nawara M, Poirier K et al. Genotype-phenotype associations for ARX gene duplication in X-linked mental retardation. Neurology 2006: 67: 2073-2075.
14. Guerrini R, Moro F, Kato M et al. Expansion of the first PolyA tract of ARX causes infantile spasms and status dystonicus. Neurology 2007: 69: 427-433.
15. Laperuta C, Spizzichino L, D'Adamo P et al. MRX87 family with Aristaless X dup24bp mutation and implication for polyAlanine expansions. BMC Med Genet 2007: 8: 25.
16. 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: 346-354.
17. Poirier K, Lacombe D, Gilbert-Dussardier B et al. Screening of ARX in mental retardation families: consequences for the strategy of molecular diagnosis. Neurogenetics 2006: 7: 39-46.
18. de Brouwer AP, Yntema HG, Kleefstra T et al. Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium. Hum Mutat 2007: 28: 207-208.
19. Kato M, Das S, Petras K, Sawaishi Y, Dobyns WB. Polyalanine expansion of ARX associated with cryptogenic West syndrome. Neurology 2003: 61: 267-276.
20. Grønskov K, Hjalgrim H, Nielsen IM, Brøndum-Nielsen K. Screening of the ARX gene in 682 retarded males. Eur J Hum Genet 2004: 12: 701-705.
21. Partington MW, Turner G, Boyle J, Gécz J. Three new families with X-linked mental retardation caused by the 428-451dup(24bp) mutation in ARX. Clin Genet 2004: 66: 39-45.
22. Poirier K, Abriol J, Souville I et al. Maternal mosaicism for mutations in the ARX gene in a family with X linked mental retardation. Hum Genet 2005: 118: 45-48.
23. Nawara M, Szczaluba K, Poirier K et al. The ARX mutations: a frequent cause of X-linked mental retardation. Am J Med Genet A 2006: 140: 727-732.
24. Reish O, Fullston T, Regev M, Heyman E, Gecz J. A novel de novo 27 bp duplication of the ARX gene, resulting from postzygotic mosaicism and leading to three severely affected males in two generations. Am J Med Genet A 2009: 149A: 1655-1660.
25. Bejerano G, Pheasant M, Makunin I et al. Ultraconserved elements in the human genome. Science 2004: 304: 1321-1325.
26. Colasante G, Collombat P, Raimondi V et al. Arx is a direct target of Dlx2 and thereby contributes to the tangential migration of GABAergic interneurons. J Neurosci 2008: 28: 10674-10686.
27. Ahituv N, Zhu Y, Visel A et al. Deletion of ultraconserved elements yields viable mice. PLoS Biol 2007: 5: e234.
28. Demos MK, Fullston T, Partington MW, Gécz J, Gibson WT. Clinical study of two brothers with a novel 33 bp duplication in the ARX gene. Am J Med Genet A 2009: 149A: 1482-1486.
29. Fullston T, Brueton L, Willis T et al. Ohtahara syndrome in a family with an ARX protein truncation mutation (c.81C>G/p.Y27X). Eur J Hum Genet 2010: 18: 157-162.
30. Shoubridge C, Tan MH, Fullston T et al. Mutations in the nuclear localization sequence of the Aristaless related homeobox; sequestration of mutant ARX with IPO13 disrupts normal subcellular distribution of the transcription factor and retards cell division. Pathogenetics 2010: 3: 1.
31. Kato M, Saitoh S, Kamei A et al. 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: 361-366.
32. Shoubridge C, Cloosterman D, Parkinson-Lawerence E, Brooks D, Gécz J. Molecular pathology of expanded polyalanine tract mutations in the Aristaless-related homeobox gene. Genomics 2007: 90: 59-71.
33. Nasrallah IM, Minarcik JC, Golden JA. A polyalanine tract expansion in Arx forms intranuclear inclusions and results in increased cell death. J Cell Biol 2004: 167: 411-416.
34. Chaste P, Nygren G, Anckarsäter H et al. Mutation screening of the ARX gene in patients with autism. Am J Med Genet B Neuropsychiatr Genet 2007: 144B: 228-230.
35. Cunningham D, Xiao Q, Chatterjee A et al. exma: an X-linked insertional mutation that disrupts forebrain and eye development. Mamm Genome 2002: 13: 179-185.
36. Whibley AC, Plagnol V, Tarpey PS et al. Fine-scale survey of X chromosome copy number variants and indels underlying intellectual disability. Am J Hum Genet 2010: 87: 173-188.
37. Yamagata K, Oda N, Kaisaki PJ et al. Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). Nature 1996: 384: 455-458.
38. Pontoglio M, Barra J, Hadchouel M et al. Hepatocyte nuclear factor 1 inactivation results in hepatic dysfunction, phenylketonuria, and renal Fanconi syndrome. Cell 1996: 84: 575-585.
39. Poirier K, Eisermann M, Caubel I et al. Combination of infantile spasms, non-epileptic seizures and complex movement disorder: a new case of ARX-related epilepsy. Epilepsy Res 2008: 80: 224-228.
40. Absoud M, Parr JR, Halliday D, Pretorius P, Zaiwalla Z, Jayawant S. A novel ARX phenotype: rapid neurodegeneration with Ohtahara syndrome and a dyskinetic movement disorder. Dev Med Child Neurol 2010: 52: 305-307.
41. Shinozaki Y, Osawa M, Sakuma H et al. Expansion of the first polyalanine tract of the ARX gene in a boy presenting with generalized dystonia in the absence of infantile spasms. Brain Dev 2009: 31: 469-472.
42. Kitamura K, Itou Y, Yanazawa M et al. Three human ARX mutations cause the lissencephaly-like and mental retardation with epilepsy-like pleiotropic phenotypes in mice. Hum Mol Genet 2009: 18: 3708-3724.
43. Albrecht A, Mundlos S. The other trinucleotide repeat: polyalanine expansion disorders. Curr Opin Genet Dev 2005: 15: 285-293.