RESUMEN
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.
Asunto(s)
Trastorno Autístico/genética , Cromosomas Humanos Par 2/genética , Predisposición Genética a la Enfermedad , Integrina alfa4/genética , Alelos , Mapeo Cromosómico , Femenino , Haplotipos/genética , Humanos , Cariotipificación , Masculino , Repeticiones de Microsatélite/genética , Mutación/genética , Linaje , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
A case of Jacobsen syndrome, suspected antenatally on the grounds of trigonocephaly and hypoplastic left heart syndrome, is presented. Clinicians are reminded that a hypoplastic left heart should not be assumed to be an isolated malformation and that a careful search for associated malformations can facilitate the recognition of an underlying genetic syndrome.