A balanced reciprocal translocation t(5;7)(q14;q32) associated with autistic disorder: Molecular analysis of the chromosome 7 breakpoint

Autism is a neuropsychiatric disorder characterized by impairments in socia l interaction, restricted and stereotypic pattern of interest with onset by 3 years of age. The results of genetic linkage studied for autistic disord er (AD) have suggested a susceptibility locus for the disease on the long a rm of chromosome 7. We report a girl with AD and a balanced reciprocal tran slocation t(5;7)(q14;q32). The mother carries the translocation but do not express the disease. Fluorescent in situ hybridization (FISH) analysis with chromosome 7-specific YAC clones showed that the breakpoint coincides with the candidate region for AD. We identified a PAC clone that spans the tran slocation breakpoint and the breakpoint was mapped to a 2 kb region. Mutati on screening of the genes SSBP and T2R3 located just centromeric to the bre akpoint was performed in a set of 29 unrelated autistic sibling pairs who s hared at least one chromosome 7 haplotype. We found no sequence variations, which predict amino acid alterations. Two single nucleotide polymorphisms were identified in the T2R3 gene, and associations between allele variants and AD in our population were not found. The methylation pattern of differe nt chromosome 7 regions in the patient's genomic DNA appears normal. Here w e report the clinical presentation of the patient with AD and the character ization of the genomic organization across the breakpoint at 7q32. The prec ise localization of the breakpoint on 7q32 may be relevant for further link age studies and molecular analysis of AD in this region. Published 2001 Wil ey-Liss, Inc.(dagger).