Chromosome 22q11.2 deletion syndrome (DiGeorge and velocardiofacial syndromes)

Perez, Elena E.; Sullivan, Kathleen E.

doi:10.1097/00008480-200212000-00005

Cited by 123 publications

(99 citation statements)

References 30 publications

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“…36 We reasoned that there could be a position effect on the expression of this gene as has been shown for other genes near chromosome breakpoints. [37][38][39][40][41][42] The role of OTX1 in sensory organ development is interesting, considering that sensory impairments are common in individuals with autism. Leekam et al 43 tested individuals with autism using the Diagnostic Interview for Social and Communication Disorders (DISCO), 44 which uses 21 items grouped in seven domains (auditory, visual, touch, smell/taste, etc.…”

Section: Discussionmentioning

confidence: 99%

2p15–p16.1 microdeletion syndrome: molecular characterization and association of the OTX1 and XPO1 genes with autism spectrum disorders

Malenfant

Reesor

et al. 2011

Eur J Hum Genet

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Reports of unrelated individuals with autism spectrum disorder (ASD) and similar clinical features having overlapping de novo interstitial deletions at 2p15-p16.1 suggest that this region harbors a gene(s) important to the development of autism. We molecularly characterized two such deletions, selecting two genes in this region, exportin 1 (XPO1) and orthodenticle homolog 1 (OTX1) for association studies in three North American cohorts (Autism Spectrum Disorder -Canadian American Research Consortium (ASD-CARC), New York, and Autism Genetic Resource Exchange (AGRE)) and one Italian cohort (Società Italiana per la Ricerca e la Formazione sull'Autismo (SIRFA)) of families with ASD. In XPO1, rs6735330 was associated with autism in all four cohorts (Po0.05), being significant in ASD-CARC cohorts (P-value following false discovery rate correction for multiple testing (P FDR )¼1.29Â10 À5 ), the AGRE cohort (P FDR ¼0.0011) and the combined families (P FDR ¼2.34Â10 À9 ). Similarly, in OTX1, rs2018650 and rs13000344 were associated with autism in ASD-CARC cohorts (P FDR ¼8.65Â10 À7 and 6.07Â10 5 , respectively), AGRE cohort (P FDR ¼0.0034 and 0.015, respectively) and the combined families (P FDR ¼2.34Â10 À9 and 0.00017, respectively); associations were marginal or insignificant in the New York and SIRFA cohorts. A significant association (P FDR ¼2.63Â10 À11 ) was found for the rs2018650G-rs13000344C haplotype. The above three SNPs were associated with severity of social interaction and verbal communication deficits and repetitive behaviors (P-values o0.01). No additional deletions were identified following screening of 798 ASD individuals. Our results indicate that deletion 2p15-p16.1 is not commonly associated with idiopathic ASD, but represents a novel contiguous gene syndrome associated with a constellation of phenotypic features (autism, intellectual disability, craniofacial/CNS dysmorphology), and that XPO1 and OXT1 may contribute to ASD in 2p15-p16.1 deletion cases and non-deletion cases of ASD mapping to this chromosome region.

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Section: Discussionmentioning

confidence: 99%

2p15–p16.1 microdeletion syndrome: molecular characterization and association of the OTX1 and XPO1 genes with autism spectrum disorders

Malenfant

Reesor

et al. 2011

Eur J Hum Genet

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“…Other syndromes occasionally associated with this deletion include conotruncal anomaly face syndrome, Opitz/GBB and CHARGE syndrome (coboloma, heart disease, atresia choanae, retarded growth and central nervous system development, genital hypoplasia and ear abnormalities and/or deafness) [2]. When all patients with chromosome 22q11.2 deletions are considered together, cardiac malformations, speech delay and immunodeficiency are the most common characteristics [3]. 22q11.2 deletion syndrome is associated with neonatal hypocalcaemia due to hypoplasia of the parathyroid glands and susceptibility to infection due to thymic hypoplasia occurs in up to 80% [2,4].…”

Section: Introductionmentioning

confidence: 99%

Immunodeficiency and Autoimmunity in 22q11.2 Deletion Syndrome

2007

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22q11.2 deletion syndrome is the commonest chromosome deletion syndrome. 22q11.2 deletion may result in variable clinical phenotypes which may differ even between patients with identical deletions. Abnormal pharyngeal arch development results in defects in the development of the parathyroid glands, thymus and conotruncal region of the heart. Defective thymic development is associated with impaired immune function. ‘Complete’ DiGeorge syndrome with total absence of the thymus and a severe T‐cell immunodeficiency accounts for <0.5% of patients. The majority of patients with 22q11.2 deletion syndromes have ‘partial’ defects with impaired thymic development rather than complete absence with variable defects in T‐cell numbers. Immunodeficiency in these patients is not solely due to T‐cell deficiency and abnormalities of T‐cell clonality or impairment of proliferative responses may play a role. Humoral deficiencies including defects in the B‐cell compartment have also been identified in these patients. 22q11.2 deletion syndrome patients are at increased risk of a variety of autoimmune diseases. A number of immune defects may predispose to the development of autoimmunity in these patients including increased infection, impaired development of natural T‐regulatory cells and impaired thymic central tolerance.

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“…As alterações imunológicas são classicamente relacionadas ao fenótipo conhecido como Síndrome de DiGeorge, mas podem manisfestar-se em qualquer um dos quadros decorrentes da deleção 22q11 e são encontradas em até 80% dos portadores (DIGEORGE, 1968;PEREZ;SULLIVAN, 2002;HAY, 2007; KOBRYNSKI; SULLIVAN, 2007). Apesar de grande parte dos pacientes apresentarem timo hipoplásico ou ausente, a maioria apresenta imunodeficiência leve à moderada, independe de outras características clínicas (SULLIVAN, 2002;PATEL et al, 2012).…”

Section: Deficiências Imunológicasunclassified

“…Também foi observado aumento na proporção de células B CD19+ e células NK nos afetados KORNFELD et al, 2000;SULLIVAN, 2007). A imunidade humoral é menos comumente comprometida, mas deficiência de IgA ocorre com maior frequência nestes indivíduos quando comparados a um grupo controle (SMITH et al, 1998;SULLIVAN et al, 1998;PEREZ;SULLIVAN, 2002;SULLIVAN, 2007).…”

Section: Deficiências Imunológicasunclassified

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Caracterização fenotípica em indivíduos com microarranjos na região cromossômica 22q11

Empke¹

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RESUMOEmpke SLL. Caracterização fenotípica em indivíduos com microarranjos na região cromossômica 22q11 [dissertação]. Bauru: Hospital de Reabilitação de Anomalias Craniofaciais, Universidade de São Paulo; 2015.Objetivo: Descrever as manifestações clínicas de indivíduos com hipótese diagnostica da Sindrome de deleção 22q11 (SD22q11) confirmados por testes genéticos, na primeira avaliação e durante o acompanhamento dos mesmos em avaliações subsequentes para uma melhor definição do curso natural da doença. Local: Laboratório de Genética e Citogenética Humana do HRAC-USP -Bauru/SP. Casuística e metodologia: O presente trabalho é retrospectivo e analisou os dados de prontuários de 72 indivíduos cadastrados no HRAC-USP, os quais receberam hipótese diagnóstica da SD22q11 e foram confirmadas por teste genético (MLPA ou FISH). A avaliação envolveu a analise dos dados relatados por todos os setores do HRAC-USP. Resultados e discussão: Foramanalisados 72prontuários deindivíduos com a SD22q11. Constatamos que a idade media dos indivíduos quando do cadastro no HRAC-USP foi de seis anos. Também constatamos que houve um longo período de tempo entre os retornos ao hospital e que, nesses retornos, nem todas as especialidades foram contempladas. Esses fatos prejudicaram a analise da historia natural da anomalia em questão. Com relação às características fenotipicas, observamos a presença de sinais clínicos típicos, como por exemplo: face alongada, lábios finos, hipoplasia alar, anormalidades menores na orelha, dígitos longos e fendas palpebrais, fissuras labiopalatinas, cardiopatias congenitas, dificuldade de aprendizagem, atraso de linguagem e distúrbios comportamentais. A fissura oral foi à manifestação otorrinolaringológica mais frequente, presente em 75% dos pacientes, onde as fissuras submucosas foram as mais frequentes (43%). As características cognitivas como, atraso de fala (87%), dificuldades de aprendizagem (95%) e distúrbios comportamentais (81%), tiveram um resultado significativo, descritas em quase todos os indivíduos. As cardiopatias congênitas estavam presentes em 47,2% dos prontuários analisados. De um modo geral, comparando a frequência dos sinais clínicos encontrados neste trabalho com dados da literatura, constatamos que as frequências encontram-se dentro do esperado. Conclusão: A maioria dos indivíduos cadastrados no HRAC-USP, pertencentes ao grupo de estudo, apresentou idade superior a 06 anos. Portanto, a observação do curso natural da historia da SD22q11 para avaliar características fenotípicas que surgissem ao longo da evolução clinica do indivíduo e que pudessem ajudar no diagnóstico, ficou prejudicada. Mesmo nos casos onde o indivíduo foi cadastrado no HRAC-USP com idade inferior a dois anos, o diagnóstico foi tardio devido a falta de uma ação multidisciplinar e interdisciplinar no hospital. Mesmo não sendo possível avaliar as características fenotípicas surgidas durante a historia natural da doença, constatamos que as manifestações clínicas relatadas nos prontuários cursam com as características da SD...

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Chromosome 22q11.2 deletion syndrome (DiGeorge and velocardiofacial syndromes)

Cited by 123 publications

References 30 publications

2p15–p16.1 microdeletion syndrome: molecular characterization and association of the OTX1 and XPO1 genes with autism spectrum disorders

2p15–p16.1 microdeletion syndrome: molecular characterization and association of the OTX1 and XPO1 genes with autism spectrum disorders

Immunodeficiency and Autoimmunity in 22q11.2 Deletion Syndrome

Caracterização fenotípica em indivíduos com microarranjos na região cromossômica 22q11

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