Comprehensive analysis of human subtelomeres with combined binary ratio labelling fluorescence in situ hybridisation.

Cryptic subtelomeric chromosome rearrangements play an important role in the aetiology of mental retardation, congenital anomalies, miscarriages and neoplasia. To facilitate a comprehensive molecular-cytogenetic analysis of these extremely gene-rich and mutation-prone chromosome regions, novel multicolour fluorescence in situ hybridisation (FISH) techniques are being developed. As yet, subtelomeric FISH methods have either had limited multiplicities, making it necessary to perform many hybridisations per patient, or a limited scope of analysable chromosome mutation types, thus not detecting some aberration types such as pericentric inversions or very small aberrations. COBRA (COmbined Binary RAtio) labelling is a generic multicolour FISH technique that combines ratio and combinatorial labelling to attain especially high multiplicities with few fluorochromes. The Subtelomere COBRA FISH method ("S-COBRA FISH") described here detects efficiently all 41 BAC and PAC FISH probes necessary for a complete subtelomere screening in only two hybridisations. It was applied to the analysis of 10 cases with known and partially known aberrations and successfully detected balanced and unbalanced translocations, deletions and an unbalanced pericentric inversion in a mosaic situation. The ability of S-COBRA FISH to efficiently detect all types of balanced and unbalanced subtelomeric chromosome aberrations makes it the most comprehensive diagnostic procedure for human subtelomeric chromosome regions described to date.

Further case of Cantú syndrome: exclusion of cryptic subtelomeric chromosome aberrations.

Cantú syndrome consists of hypertrichosis, osteochondrodysplasia, and cardiomegaly, and has been reported in 18 patients to date. We report an infant with Cantú syndrome. In addition to typical findings, he had relatively mild radiological and cardiological manifestations. Previously undescribed findings included pyloric stenosis and elevated alkaline phosphatase levels. Brain scans showed bilateral calcification of the Arteriae thalamostriatae and widening of the outer liquor spaces and lateral ventricles. Because the propositus is the youngest patient reported to date, our findings refine the clinical spectrum of Cantú syndrome in neonates and young infants. The etiology and mode of inheritance of Cantú syndrome are unknown. Most cases are sporadic. Microdeletions have been discussed as a possible cause of Cantú syndrome. Recently, several syndromes with multiple congenital anomalies and mental retardation have been shown to be caused by subtelomeric chromosome aberrations. We excluded the presence of a cryptic subtelomeric chromosome anomaly in our patient by fluorescence in situ hybridization (FISH) screening with locus-specific probes.