PURPOSE: A number of genes in the 9q34.11 region may be haploinsufficient. 
However, studies analyzing genotype-phenotype correlations of deletions 
encompassing multiple dosage-sensitive genes in the region are lacking.
METHODS: We mapped breakpoints of 10 patients with 9q34.11 deletions using 
high-resolution 9q34-specific array comparative genomic hybridization (CGH) to 
determine deletion size and gene content.
RESULTS: The 9q34.11 deletions range in size from 67 kb to 2.8 Mb. Six patients 
exhibit intellectual disability and share a common deleted region including 
STXBP1; four manifest variable epilepsy. In five subjects, deletions include 
SPTAN1, previously associated with early infantile epileptic encephalopathy, 
infantile spasms, intellectual disability, and hypomyelination. In four 
patients, the deletion includes endoglin (ENG), causative of hereditary 
hemorrhagic telangiectasia. Finally, in four patients, deletions involve TOR1A, 
of which molecular defects lead to early-onset primary dystonia. Ninety-four 
other RefSeq genes also map to the genomic intervals investigated.
CONCLUSION: STXBP1 haploinsufficiency results in progressive encephalopathy 
characterized by intellectual disability and may be accompanied by epilepsy, 
movement disorders, and autism. We propose that 9q34.11 genomic deletions 
involving ENG, TOR1A, STXBP1, and SPTAN1 are responsible for multisystemic 
vascular dysplasia, early-onset primary dystonia, epilepsy, and intellectual 
disability, therefore revealing cis-genetic effects leading to complex 
phenotypes.