A balanced t(10;15) translocation in a male patient with developmental language disorder.

We report the clinical and cytogenetic findings on a male child with developmental language disorder, no physical abnormalities, and a balanced t(10;15)(q24.1;q21.1) translocation. As the child's parents are unavailable for investigations, it is unclear whether the translocation is inherited or de novo. Fluorescence in situ hybridization (FISH) analyses were carried out using specific RP11-BAC clones mapping near 15q21.1 and 10q24.1 to refine the location of the breakpoints. The breakpoint on 15q21.1 interrupts the SEMA6D gene and the breakpoint on 10q24.1 is located between the ENTPD1 and CCNJ genes. The SEMA6D gene was further investigated in samples of individuals with developmental language disorders and controls; this investigation offered further evidence of the involvement of SEMA6D with developmental language disorders.

Atopic features in early childhood autism.

BACKGROUND: Autism is a developmental disorder of unknown etiology. Sensitivity to dietary and environmental antigens has been considered in its pathogenesis. AIM: To examine immediate hypersensitivity in early childhood autism. METHODS: We investigated 30 autistic children (23 boys, seven girls 2-4 years old) for atopic history, serum IgG, IgA, IgM, IgE levels, and skin prick tests (SPT) with 12 common antigens. RESULTS: Nine/30 autistic children (30%) and 1/39 (2.5%) age-matched neurological controls from the same hospital had a family history suggestive of atopy (p<0.005). No patient in the autism and 28% in control group had symptoms of respiratory allergy (wheezing or asthma) (p<0.005), and 6/30 (20%) autistic vs. 7/39 (17%) control children had history suggesting other allergic disorders (p=ns). Eleven/23 (47.8%) autistic children had at least one positive skin test, similar to age-matched population controls. Serum IgG, IgA, and IgM levels were within age-appropriate limits. Serum IgE was elevated in four patients (13.3%). Specific IgE levels were negative in four cases with multiple SPT positivity. CONCLUSIONS: This study suggests allergic features based on history, skin tests, and serum IgE levels are not frequent in young autistic children despite family history. This discrepancy between predisposition and manifestation might imply immunological factors or environmental conditions.

Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders.

Autism spectrum disorders (ASD) are a group of related neurodevelopmental syndromes with complex genetic etiology. We identified a de novo chromosome 7q inversion disrupting Autism susceptibility candidate 2 (AUTS2) and Contactin Associated Protein-Like 2 (CNTNAP2) in a child with cognitive and social delay. We focused our initial analysis on CNTNAP2 based on our demonstration of disruption of Contactin 4 (CNTN4) in a patient with ASD; the recent finding of rare homozygous mutations in CNTNAP2 leading to intractable seizures and autism; and in situ and biochemical analyses reported herein that confirm expression in relevant brain regions and demonstrate the presence of CNTNAP2 in the synaptic plasma membrane fraction of rat forebrain lysates. We comprehensively resequenced CNTNAP2 in 635 patients and 942 controls. Among patients, we identified a total of 27 nonsynonymous changes; 13 were rare and unique to patients and 8 of these were predicted to be deleterious by bioinformatic approaches and/or altered residues conserved across all species. One variant at a highly conserved position, I869T, was inherited by four affected children in three unrelated families, but was not found in 4010 control chromosomes (p = 0.014). Overall, this resequencing data demonstrated a modest nonsignificant increase in the burden of rare variants in cases versus controls. Nonetheless, when viewed in light of two independent studies published in this issue of AJHG showing a relationship between ASD and common CNTNAP2 alleles, the cytogenetic and mutation screening data suggest that rare variants may also contribute to the pathophysiology of ASD, but place limits on the magnitude of this contribution.

Apparently novel genetic syndrome of pachygyria, mental retardation, seizure, and arachnoid cysts.

We report on an apparently new syndrome in a consanguineous family with seven members, three of whom have cerebral anomalies including pachygyria and arachnoid cysts along with mental retardation and seizures. The two patients with seizure disorders also had multiple enlarged perivascular spaces seen in the white matter of the centrum semiovale. Our data provide a contribution to the accumulating knowledge on familial cerebral anomalies including arachnoid cysts and lissencephaly. Given the lack of mutation in known lissencephaly genes such as LIS1, 14-3-3epsilon, and DCX, this syndrome may constitute a new phenotype with autosomal recessive inheritance.