Clinical utility of array comparative genomic hybridization: uncovering tumor susceptibility in individuals with developmental delay.

Microarray-based comparative genomic hybridization can determine genome-wide copy number alterations at the kilobase level. We highlight the clinical utility of microarray-based comparative genomic hybridization in determining tumor susceptibility in 3 patients with dysmorphic features and developmental delay, likely decreasing both morbidity and mortality in these patients.

Mechanisms and consequences of small supernumerary marker chromosomes: from Barbara McClintock to modern genetic-counseling issues.

Supernumerary marker chromosomes (SMCs) are common, but their molecular content and mechanism of origin are often not precisely characterized. We analyzed all centromere regions to identify the junction between the unique chromosome arm and the pericentromeric repeats. A molecular-ruler clone panel for each chromosome arm was developed and used for the design of a custom oligonucleotide array.

Genotype/phenotype correlations in two patients with 12q subtelomere deletions.

Subtelomeric imbalances have been implicated in developmental delay and mental retardation (MR) and described for most chromosomes. This study reports the first detailed description of two individuals with de novo 12q subtelomere deletions and high-resolution mapping of their deletion size with oligonucleotide array CGH for genotype/phenotype comparisons. Patient 1 is an 8-year-old male with borderline mild MR, food-seeking behavior, obesity, no significant dysmorphic facial features, abnormal hair whorl pattern, brachydactyly and mild clinodactyly.

The evolution of molecular ruler analysis for characterizing telomere imbalances: from fluorescence in situ hybridization to array comparative genomic hybridization.

Submicroscopic telomere imbalances are a significant cause of mental retardation with or without other phenotypic abnormalities. We previously developed a set of unique telomere clones that identify imbalances in 3% to 5% of children with unexplained mental retardation and a normal karyotype. This targeted screening approach, however, does not provide information about the size or gene content of the imbalance.