Infantile spasms, dystonia, and other X-linked phenotypes caused by mutations in Aristaless related homeobox gene, ARX

Strømme, Petter; Mangelsdorf, Marie; Scheffer, Ingrid E.; Gécz, Jozef

doi:10.1016/s0387-7604(02)00079-7

Cited by 187 publications

(143 citation statements)

References 9 publications

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“…Furthermore, the Dlx genes regulate the expression of the X-linked Arx gene in basal ganglia progenitor cell populations, 41 and a subset of patients with a mutation of ARX gene have autistic features. 42,43 Both the neuropathological findings, which indicate altered organization of specific regions of the brain 44 -46 and the co-occurrence of autism with a number of neurological and cognitive disorders, including epilepsy, 8 support a role for the DLX gene complexes in interneuron development and GABAergic-mediated pathophysiological changes that are central components of autism. 47 We had only a small group of individuals (n ¼ 32) with confirmed seizures.…”

Section: Discussionmentioning

confidence: 96%

The DLX1and DLX2 genes and susceptibility to autism spectrum disorders

Novosedlik

Wang

et al. 2008

Eur J Hum Genet

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An imbalance between excitation and inhibition in the cerebral cortex has been suggested as a possible etiology of autism. The DLX genes encode homeodomain-containing transcription factors controlling the generation of GABAergic cortical interneurons. The DLX1 and DLX2 genes lie head-to-head in 2q32, a region associated with autism susceptibility. We investigated 6 Tag SNPs within the DLX1/2 genes in two cohorts of multiplex (MPX) and one of simplex (SPX) families for association with autism. Family-based association tests showed strong association with five of the SNPs. The common alleles of rs743605 and rs4519482 were significantly associated with autism (Po0.012) in the first sample of 138 MPX families, with the latter remaining significant after correction for multiple testing (P cor ¼ 0.0046). Findings in a second sample of 169 MPX families not only confirmed the association at rs4519482 (P ¼ 0.034) but also showed strong allelic association of the common alleles at rs788172, rs788173 and rs813720 (P cor ¼ 0.0003 -0.04). In the combined MPX families, the common alleles were all significantly associated with autism (P cor ¼ 0.0005-0.016). The GGGTG haplotype was over transmitted in the two MPX cohorts and the combined samples [P cor o0.05: P cor ¼ 0.00007 for the combined MPX families, Odds Ratio: 1.75 (95% CI: 1.33 -2.30)]. Further testing in 306 SPX families replicated the association at rs4519482 (P ¼ 0.033) and the over transmission of the haplotype GGGTG (P ¼ 0.012) although P-values were not significant after correction for multiple testing. The findings support the presence of two functional polymorphisms, one in or near each of the DLX genes that increase susceptibility to, or cause, autism in MPX families where there is a greater genetic component for these conditions.

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Section: Discussionmentioning

confidence: 96%

The DLX1and DLX2 genes and susceptibility to autism spectrum disorders

Novosedlik

Wang

et al. 2008

Eur J Hum Genet

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“…Conforme se amplia o conhecimento acerca da sW e dos métodos complementares de diagnóstico, haverá tendência à diminuição dos casos hoje considerados criptogênicos ou idiopáticos. um exemplo claro disso é a descoberta recente da mutação no gene Aristaless-related homeobox (ARX) como causa de sW ligada ao cromossomo X 11 . o exame que detecta a mutação no gene ARX ainda não é disponível em nosso meio.…”

Section: Fig 1 Gráfico Da Distribuição Dos Pacientes Com Sw Em Casosunclassified

Possíveis etiologias da Síndrome de West: avaliação de 95 pacientes

Matta¹,

Chiacchio²,

Leyser³

2007

Arq. Neuro-Psiquiatr.

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Resumo -Objetivo: Descrever as etiologias da síndrome de West (sW) em um grupo de crianças atendidas no ambiente de um centro de reabilitação. Método: Análise retrospectiva, avaliando-se os seguintes itens: gênero, idade por ocasião da definição do diagnóstico da sW e sua etiologia. esta foi dividida em três categorias: sintomática, criptogênica e idiopática. os casos sintomáticos foram divididos em pré, peri e pós-natais. Resultados: Noventa e cinco pacientes foram incluídos, sendo 59 do gênero masculino (62%). A idade do diagnóstico variou entre 1 e 24 meses, com média de 4,9 (±5,0) meses. Vinte e cinco casos foram considerados criptogênicos (26,3%) e apenas um idiopático (1,1%). os demais foram classificados com sintomáticos (72,6%), sendo predominantemente casos perinatais. Conclusão: Nossos achados se assemelham aos da literatura. Conforme se ampliam o conhecimento acerca da sW e os métodos complementares de diagnóstico, haverá tendência à diminuição dos casos hoje considerados criptogênicos ou idiopáticos.PAlAVRAs-ChAVe: síndrome de West, epilepsia, etiologia. Possible etiologies of West syndrome: evaluation of 95 patientsAbstRACt -Objective: to describe the etiologies of West syndrome (Ws) among children followed in a rehabilitation center. Method: Retrospective study with emphasis in the following items: gender, age at the diagnosis of Ws and its etiology. the etiologies were divided into three categories: symptomatic, cryptogenic and idiopathic. symptomatic cases were classified as follows: pre, post and perinatal. Results: Ninety-five patients were included. Fifty-nine were boys (62%). mean age at the diagnosis was 4.9 (±5.0) months. there were 25 cryptogenic (26.3%), one idiopathic (1.1%) and 69 (72.6%) symptomatic cases, most of them of perinatal origin. Conclusion: our findings are in agreement with the literature. In the future, as our knowledge in the field of Ws and its diagnostic methods increase, there will be a small number of cryptogenic and idiopathic cases.Key WoRDs: West syndrome, epilepsy, etiology.Rede sarah de hospitais de Reabilitação-Centro de Reabilitação Infantil evandro Carlos de Andrade, Rio de Janeiro RJ, brasil: 1 Neurologista; 2 Anestesiologista; 3 Pediatra. em 1841, o médico inglês William James West descreveu em seu próprio filho uma síndrome caracterizada por salvas de espasmos, durante as quais sua cabeça era projetada anteriormente em direção aos joelhos. em seguida, havia um relaxamento, voltando-se à posição normal. havia três ou mais ataques como esse ao longo do dia, durando cerca de dois a três minutos cada 1 . Cerca de 100 anos mais tarde, a correspondência eletrencefalográfica destas crises foi descrita, recebendo o nome de hipsarritmia. esta se define como uma atividade elétrica cerebral caótica, polimórfica, de grande amplitude e baixa freqüên-cia (ritmos delta e teta) e com espículas multifocais superimpostas 2 . o epônimo síndrome de West (sW) foi criado por Gastaut e colaboradores, na década de 1960 2 , para descrever esta condição, que hoje é universalmente re...

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“…Among others, polyalanine tract expansion mutations have been detected. One of them, the dup24bp mutation (Strømme et al, 2002a), is so far the most frequent mutation causing nonsyndromic mental retardation and shows the widest range of clinical presentations (Strømme et al, 2002b). Although the pathogenic role of the expanded polyalanine tracts is not deciphered yet, it is unlikely that they would cause protein aggregation seen in the other dominant disorders due to polyalanine and polyglutamine expansions.…”

Section: Introductionmentioning

confidence: 99%