High-resolution SNP array analysis of patients with developmental disorder and normal array CGH results.

BACKGROUND: Diagnostic analysis of patients with developmental disorders has improved over recent years largely due to the use of microarray technology. Array methods that facilitate copy number analysis have enabled the diagnosis of up to 20% more patients with previously normal karyotyping results. A substantial number of patients remain undiagnosed, however. METHODS AND RESULTS: Using the Genome-Wide Human SNP array 6.0, we analyzed 35 patients with a developmental disorder of unknown cause and normal array comparative genomic hybridization (array CGH) results, in order to characterize previously undefined genomic aberrations. We detected no seemingly pathogenic copy number aberrations. Most of the vast amount of data produced by the array was polymorphic and non-informative. Filtering of this data, based on copy number variant (CNV) population frequencies as well as phenotypically relevant genes, enabled pinpointing regions of allelic homozygosity that included candidate genes correlating to the phenotypic features in four patients, but results could not be confirmed. CONCLUSIONS: In this study, the use of an ultra high-resolution SNP array did not contribute to further diagnose patients with developmental disorders of unknown cause. The statistical power of these results is limited by the small size of the patient cohort, and interpretation of these negative results can only be applied to the patients studied here. We present the results of our study and the recurrence of clustered allelic homozygosity present in this material, as detected by the SNP 6.0 array.

Array CGH in molecular diagnosis of mental retardation - A study of 150 Finnish patients.

We report on the results of an array comparative genomic hybridization (array CGH) study of 150 karyotypically normal Finnish patients with idiopathic mental retardation and/or dysmorphic features and/or malformations. Using high-resolution microarray analysis, we sought to identify clinically relevant microdeletions and microduplications in these patients. The results were confirmed using other methods and compared with findings reported in recent publications and internet databases. Small aberrations of potential clinical significance were found in 28 (18.6%) of the 150 patients. Eight of the identified aberrations are known to cause syndromes, 4 affected the X chromosome in males, 4 were familial, and 13 have yet to be associated with a phenotype. This study demonstrates the benefits of array CGH in clinical diagnostics of developmental disorders. Further, our findings give evidence of new syndromes.