Recent array-based studies have detected a wealth of copy number variations (CNVs) in patients with autism spectrum disorders (ASD). Since CNVs also occur in healthy individuals, their contributions to the patient’s phenotype remain largely unclear. In a cohort of children with symptoms of ASD, diagnosis of the index patient using ADOS-G and ADI-R was performed, and the Social Responsiveness Scale (SRS) was administered to the index patients, both parents, and all available siblings. CNVs were identified using SNP arrays and confirmed by FISH or array CGH. To evaluate the clinical significance of CNVs, we analyzed three families with multiple affected children (multiplex) and six families with a single affected child (simplex) in which at least one child carried a CNV with a brain-transcribed gene. CNVs containing genes that participate in pathways previously implicated in ASD, such as the phosphoinositol signaling pathway (PIK3CA, GIRDIN), contactin-based networks of cell communication (CNTN6), and microcephalin (MCPH1) were found not to co-segregate with ASD phenotypes. In one family, a loss of CNTN5 co-segregated with disease. This indicates that most CNVs may by themselves not be sufficient to cause ASD, but still may contribute to the phenotype by additive or epistatic interactions with inherited (transmitted) mutations or non-genetic factors. Our study extends the scope of genome-wide CNV profiling beyond de novo CNVs in sporadic patients and may aid in uncovering missing heritability in genome-wide screening studies of complex psychiatric disorders.

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Renal-cell carcinomas (RCC) are clinically, histologically and cytogenetically very heterogeneous. The present histological WHO classification shows no clear correlation between histologic subtypes and specific chromosomal abnormalities. In 1986, a new classification was proposed by Thoenes and Störkel based on the cell type from which the tumor arises. They distinguish 5 cell types: clear-cell, chromophilic, chromophobic, ductus Bellini and oncocytic. Results of 105 primary tumors show that, in this new classification, there is a correlation between different subtypes of renal-cell tumor and specific chromosomal abnormalities at a microscopic and/or molecular level. The clear-cell compact type shows structural aberrations of chromosomes I, 3, 4, 5q, 6, 10q, 11q and 12q, together with polysomy of chromosomes X, 4, 5, 7, 10, 12, 15, 16, 19, 20, 21 and 22, monosomy of chromosomes 3, 8, 9, 13, 14, and loss of Y. The main characteristics of the chromophilic tubulo-papillary type are trisomies 7 and 17, and loss of the Y-chromosome. Chromophobic carcinoma seems to be correlated with, inter alia, polysomy 7, trisomies 12, 16, 18, 19, structural abnormalities of 11q, and telomeric associations. Oncocytomas do not reveal any specific chromosomal anomaly, except for trisomy 7. Loss of heterozygosity on 3p is only found in the clear-cell compact type. Some specific chromosomal abnormalities correlate with a particular grade of the tumor. These correlations support the hypothesis that specific chromosomal abnormalities play a role in the histogenesis and oncogenesis of RCC. They may be important for tumor diagnosis and clinical prognosis.