Language endangerment and language documentation in Africa

Non peer reviewe

Fine mapping and association studies in a candidate region for autism on chromosome 2q31-q32

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

The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients

International audienceThe 2q37 locus is one of the most commonly deleted subtelomeric regions. Such a deletion has been identified in >100 patients by telomeric fluorescence in situ hybridization (FISH) analysis and, less frequently, by array-based comparative genomic hybridization (array-CGH). A recognizable ‘2q37-deletion syndrome’ or Albright’s hereditary osteodystrophy-like syndrome has been previously described. To better map the deletion and further refine this deletional syndrome, we formed a collaboration with the Association of French Language Cytogeneticists to collect 14 new intellectually deficient patients with a distal or interstitial 2q37 deletion characterized by FISH and array-CGH. Patients exhibited facial dysmorphism (13/14) and brachydactyly (10/14), associated with behavioural problems, autism or autism spectrum disorders of varying severity and overweight or obesity. The deletions in these 14 new patients measured from 2.6 to 8.8 Mb. Although the major role of HDAC4 has been demonstrated, the phenotypic involvement of several other genes in the deleted regions is unknown. We further refined the genotype–phenotype correlation for the 2q37 deletion. To do this, we examined the smallest overlapping deleted region for candidate genes for skeletal malformations (facial dysmorphism and brachydactyly), overweight, behavioural problems and seizures, using clinical data, a review of the literature, and the Manteia database. Among the candidate genes identified, we focus on the roles of PRLH, PER2, TWIST2, CAPN10, KIF1A, FARP2, D2HGDH and PDCD1