RESUMO
Autism (OMIM %209850) is a neurodevelopmental disorder with a strong genetic component. We previously reported a de novo rearrangement of chromosome 2q31 in a patient with autism [Gallagher et al. (2003); J Autism Dev Disord 33(1):105-108]. Further cytogenetic analysis revealed this to be a 46,XY, t(9;2)(q31.1;q32.2q31.3) translocation. Association mapping with microsatellite and SNP markers of this translocated region on 2q revealed association with markers in Integrin alpha-4 (ITGA4; GeneID 3676). ITGA4 was tested for association in a sample of 179 trio-based families. SNP markers in exons 16 and 17 showed evidence of association. Mutation screening revealed a G to A synonymous variation in the last nucleotide of exon 16 (rs12690517), significantly associated with autism in the Irish sample (OR = 1.6; P = 0.04). The location of this SNP at a putative splice donor site may affect the splicing of the ITGA4 protein. Haplotype analysis showed significant overtransmission of haplotypes surrounding this marker. These markers were investigated in two additional samples, 102 families from Vanderbilt University (VT) (n = 102), and AGRE (n = 267). A non-significant trend towards overtransmission of the associated allele of rs12690517 in the Irish sample (OR = 1.2; P = 0.067) and haplotypes at the 3' end of ITGA4 was observed in the AGRE sample. The VT sample showed association with markers and haplotypes across the gene, but no association with the rs12690517 marker or its surrounding haplotypes. The combined sample showed evidence of association with rs12690517 (OR = 1.3; P = 0.008) and surrounding haplotypes. The findings indicate some evidence for the role of ITGA4 as candidate gene for autism.
Assuntos
Transtorno Autístico/genética , Cromossomos Humanos Par 2/genética , Predisposição Genética para Doença , Integrina alfa4/genética , Alelos , Mapeamento Cromossômico , Feminino , Haplótipos/genética , Humanos , Cariotipagem , Masculino , Repetições de Microssatélites/genética , Mutação/genética , Linhagem , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Terminal deletion of chromosome 4q is a genetic abnormality associated predominantly with cardiac abnormalities, abnormal facial features, and developmental delay. A specific clinical clue to this infrequently diagnosed disorder is hypoplasia of the terminal phalanx of the fifth finger with an abnormal nail, occasionally extending onto the volar surface. Ocular manifestations of the disorder are uncommon, but anterior segment dysgenesis and glaucoma have been described with proximal deletions of chromosome 4 with phenotypes resembling Rieger's anomaly. We present a case of 4q deletion syndrome, presenting with asymptomatic bilateral disk swelling.
Assuntos
Anormalidades Múltiplas/genética , Deleção Cromossômica , Cromossomos Humanos Par 4/genética , Papiledema/congênito , Anormalidades Múltiplas/diagnóstico , Pré-Escolar , Anormalidades Craniofaciais/diagnóstico , Feminino , Dedos/anormalidades , Cardiopatias Congênitas/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Unhas Malformadas/genética , Papiledema/diagnóstico , Síndrome , Tomografia Computadorizada por Raios XRESUMO
Autism is a neurodevelopmental disorder presenting in the first 3 years of life. Deficits occur in the three core areas of communication, social interaction, and behavior. The causes of autism are unknown, but clinical genetic studies show strong evidence in favor of a genetic etiology. Molecular genetic studies report some association with candidate genes, and candidate regions have emerged from several genome-wide linkage studies. Here we report a clinical case of autism with a deletion on chromosome 2 in a young male with high-functioning autism. The deletion seems to correspond with regions emerging from linkage studies. We propose this as a possible candidate region in the search for autism genes.
Assuntos
Transtorno Autístico/genética , Cromossomos Humanos Par 2/genética , Deleção de Genes , Adolescente , Citogenética/métodos , Humanos , Cariotipagem , Masculino , Mutação Puntual/genéticaRESUMO
A recent report identified bipolar affective disorder in a patient with a de novo deletion 11q24.2. We record a further instance involving this cytogenetic region and bipolar affective disorder in a patient with a balanced translocation.