Although the dominant approach posits that developmental dyslexia arises from deficits in systems that are exclusively linguistic in nature (i.e., phonological deficit theory), dyslexics show a variety of lower level deficits in sensory and attentional processing. Although their link to the reading disorder remains contentious, recent empirical and computational studies suggest that spatial attention plays an important role in phonological decoding. The present behavioral study investigated exogenous spatial attention in dyslexic children and matched controls by measuring RTs to visual and auditory stimuli in cued-detection tasks. Dyslexics with poor nonword decoding accuracy showed a slower time course of visual and auditory (multisensory) spatial attention compared with both chronological age and reading level controls as well as compared with dyslexics with slow but accurate nonword decoding. Individual differences in the time course of multisensory spatial attention accounted for 31% of unique variance in the nonword reading performance of the entire dyslexic sample after controlling for age, IQ, and phonological skills. The present study suggests that multisensory “sluggish attention shifting”—related to a temporoparietal dysfunction—selectively impairs the sublexical mechanisms that are critical for reading development. These findings may offer a new approach for early identification and remediation of developmental dyslexia.

Focused visuo-spatial attention was studied in 10 developmental dyslexic children with impaired nonword reading, 10 dyslexic children with intact nonword reading, and 12 normally reading children. Reaction times to lateralized visual stimuli in a cued detection task showed that attentional facilitation of the target at the cued location was symmetrical in the three groups. However, dyslexics with impaired nonword reading selectively showed a lack of attentional inhibition for targets at the uncued location in the right visual field. This result was replicated in a second group of 13 dyslexics with impaired nonword reading. Individual differences in the ability of right attentional inhibition across the entire sample of dyslexics accounted for 17% of unique variance in nonword reading accuracy after controlling for individual differences in age, IQ, and phonological skills. A possible explanation based on the role of spatial attention mechanisms in the graphemic parsing process is discussed. Our results suggest that focused visuo-spatial attention may be crucial for nonword decoding.

In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%), ring chromosomes (14%), and unbalanced translocations (7%). We also discovered interstitial deletions between 17–74 kb in 9% of the patients. Haploinsufficiency of the SHANK3 gene, confirmed in all rearrangements, is very likely the cause of the major neurological features associated with PMS. SHANK3 mutations can also result in language and/or social interaction disabilities. We determined the breakpoint junctions in 29 cases, providing a realistic snapshot of the variety of mechanisms driving non-recurrent deletion and repair at chromosome ends. De novo telomere synthesis and telomere capture are used to repair terminal deletions; non-homologous end-joining or microhomology-mediated break-induced replication is probably involved in ring 22 formation and translocations; non-homologous end-joining and fork stalling and template switching prevail in cases with interstitial 22q13.3. For the first time, we also demonstrated that distinct stabilizing events of the same terminal deletion can occur in different early embryonic cells, proving that terminal deletions can be repaired by multistep healing events and supporting the recent hypothesis that rare pathogenic germline rearrangements may have mitotic origin. Finally, the progressive clinical deterioration observed throughout the longitudinal medical history of three subjects over forty years supports the hypothesis of a role for SHANK3 haploinsufficiency in neurological deterioration, in addition to its involvement in the neurobehavioral phenotype of PMS. Terminal chromosome deletions are among the most commonly observed rearrangements detected by cytogenetics and may result in several well-known genetic syndromes. We used 22q13 deletions to study how these types of chromosome abnormalities arise. Children with Phelan/McDermid syndrome, caused by deletion of the terminal portion of chromosome 22, experience developmental delay, absent or severely delayed speech, and frequent behavioral problems. Lack of one copy of SHANK3, a key gene for the correct development and organization of brain synapses, is very likely the basis of the syndrome's major neurological features. Deletion of additional genes probably causes more complex phenotypes in subjects with larger deletions. We also studied patients who only lack a portion of SHANK3 and demonstrated that small, hard-to-detect deletions of this gene may cause substantial clinical problems. Until now, the 22q distal deletion had been only diagnosed in very young people. We studied a large group of patients of different ages and discovered that all adult patients face progressive cognitive decline. Our study demonstrates that deletion of the terminal portion of chromosome 22, a prototype for terminal deletions in human chromosomes, can occur in several ways. Mosaic deletions of different size can also form in early embryogenesis.