Subtelomere FISH analysis of 11 688 cases: an evaluation of the frequency and pattern of subtelomere rearrangements in individuals with developmental disabilities

• Published in: Journal of medical genetics Vol. 43; no. 6; pp. 478 - 489
• Main Authors: Ravnan, J B, Tepperberg, J H, Papenhausen, P, Lamb, A N, Hedrick, J, Eash, D, Ledbetter, D H, Martin, C L
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.06.2006; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adolescent; Adult; Biological and medical sciences; Cardiology. Vascular system; Child; Child, Preschool; Chromosome Aberrations; Cloning; CNP; Confidence intervals; copy number polymorphism; Cytogenetics; Developmental Disabilities - diagnosis; Developmental Disabilities - genetics; Female; FISH; fluorescence in situ hybridisation; General aspects. Genetic counseling; Genetic Testing; Genomes; Genotype & phenotype; Humans; In Situ Hybridization, Fluorescence; Infant; Intellectual disabilities; Laboratories; Male; Medical genetics; Medical sciences; mental retardation; Original; Phenotype; Retrospective Studies; Studies; subtelomere; telomere; Telomere - chemistry; variant; Case study; Human; Evaluation; Fluorescence in situ hybridization; Frequency; Genetics; Developmental disorder
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2005.036350

Background: Subtelomere fluorescence in situ hybridisation (FISH) analysis has increasingly been used as an adjunct to routine cytogenetic testing in order to detect small rearrangements. Previous reports have estimated an overall abnormality rate of 6%, with a range of 2–29% because of different inclusion criteria. Methods: This study presents data compiled from 11 688 cases referred for subtelomere FISH testing in three clinical cytogenetic laboratories. Results: In this study population, the detection rate for clinically significant subtelomere abnormalities was approximately 2.5%, with an additional 0.5% detection of presumed familial variants. Approximately half of the clinically significant abnormalities identified were terminal deletions, the majority of which were de novo. Most of the remaining cases were unbalanced translocations between two chromosomes or two arms of the same chromosome. Approximately 60% of the unbalanced translocations were inherited from a parent carrying a balanced form of the rearrangement. Other abnormalities identified included tandem duplications, apparently balanced translocations, partial deletions, and insertions. Interestingly, 9 cases (0.08%) were found to have interstitial deletions of non-telomeric control loci, either BCR on 22q or PML on 15q. The most common clinically significant imbalances found were deletions of 1p, 22q, 4p, 9q, 8p, 2q and 20p. The most common familial variants were a deletion or duplication of 10q, deletion of 4q, deletion of Yq, and duplication of X/Yp onto Xq. Conclusions: This study of subtelomere rearrangements is a 20 fold increase in number over the previously reported largest study and represents an unbiased analysis of subtelomere rearrangements in a large, unselected patient population.