Abstract
Mental retardation (MR), defined as an intelligence quotient (IQ) less than 70, represents the most frequent serious handicap in children and young adults. Moderate to severe MR (IQ<50) encompasses 1% of the population and the prevalence increases up to 2–3% if mild mental retardation (50<IQ<70) is included (1,2). Mental retardation may result from multiple causal factors: environmental factors (fetal alcohol syndrome or perinatal hypoxic-ischaemic damage for example), chromosomal factors (such as trisomy 21), or monogenic diseases (Fra-X syndrome for example). Chromosomal abnormalities, such as deletions, duplications or uniparental disomies (UPD) that result in an alteration of normal gene dosage, are a common cause of mental retardation found in 12% of a random series of mentally retarded patients (3). The responsible chromosomal segment is usually small (< 10 Mb), but encompasses multiple genes which contribute to the phenotype independently. Routine chromosome analysis allows detection of duplications and deletions in the 10 Mb range, and therefore remains above the threshold for phenotypic effect. Despite numerous attempts to increase reliability and resolution, there is still no practical way to screen the entire genome for rearrangements, regardless of size or chromosomal localization.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Rutter M., Tizard J., and Whitmore K. (1970) Education, Health and Behaviour. Longman, London.
Crow Y. J. and Tolmie J. L. (1998) Recurrence risks in mental retardation. J. Med. Genet. 35, 177–182.
Curry C. J., Stevenson R. E., Aughton D., et al. (1997) Evaluation of mental retardation: recommendations of a consensus conference. Am. J. Med. Genet. 72, 468–477.
Gustavson K. H., Hagberg B., Hagberg G., and Sars K. (1977 ) Severe mental retardation in a Swedish county: II, etiologic and pathogenetic aspects of children born 1959-1970. Neuropediatry 8, 293–304.
Elwood J. H. and Darragh P. M. (1973) Severe mental handicap in Northern Ireland. J. Mental. Defic. Res. 25, 147–155.
Flint J., Wilkie A. O. M., Buckle V. J., Winter R. M., Holland A. J., and McDermid H. E. (1995) The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nat. Genet. 9, 132–140.
Knight S. J. L., Horsley S. W., Regan R., et al. (1997) Development and clinical application of an innovative fluorescence in situ hybridization technique which detects submicroscopic rearrangements involving telomeres. Eur. J. Hum. Genet. 5, 1–8.
Knight S. J. L., Regan R., Nicod A., et al. (1999). Subtle chromosomal rearrangements in children with unexplained mental retardation. Lancet 54, 1676–1681.
Ledbetter D. H. and Ballabio A. (1995) Molecular cytogenetics of contigous gene syndromes: Mechanisms and consequences of gene dosage imbalances; In The metabolic and molecular bases of inherited disease. Vol 1. (Scriver C. R., Beaudet A. L., Sly W. S., and Valle D., eds.), McGraw-Hill, New York, pp. 811–839.
Mazzarella R. and Schlessinger D. (1998) Pathological consequences of sequence duplications in the human genome. Genome Res. 8, 1007–1021.
Kallionemi A., Kallionemi O. P., and Sudar D. (1992) Comparative Genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258, 818–821.
Du Manoir S., Speicher M. R., Joos S., et al. (1993) Detection of complete and partial chromosomal gains and losses by comparative genomic in situ hybridization. Hum. Genet. 90, 590–610.
Ghaffari S. R., Boyd E., Tolmie J. L., Crow Y. J., Trainer A. H., Connor J. M. (1998) A new strategy for cryptic telomeric translocation screening in patients with idiopathic mental retardation. J. Med. Genet. 35, 225–233.
Slavotinek A., Rosenberg M., Knight S., et al. (1999) Screening for submicroscopic chromosome rearrangements in children with idiopathic mental retardation using microsatellite markers for the chromosome telomeres. J. Med. Genet. 36, 405–411.
Colleaux L., Rio M., Heuertz S., et al. (2001) A novel automated strategy for screening cryptic telometric rearrangements in children with idiopathic mental retardation. Eur. J. Hum. Genet. 9, 319–327.
Wilkie A. O., Zeitlin H. C., Lindenbaum R. H., et al. (1990) Clinical features and molecular analysis of the alpha thalassemia/mental retardation syndromes. I. cases due to deletions involving chromosome band 16p13.3. Am. J. Hum. Genet. 46, 1112–1126.
Goodship J., Curtis A., Cross I., et al. (1992) A submicroscopic translocation, t(4;10), responsible for recurrent Wolf-Hirschhorn syndrome identified by allele loss and fluorescent in situ hybridization. J. Med. Genet. 29, 451–454.
Kuwano A., Ledbetter S. A., Dobyns W. B., Emanuel B. S., and Ledbetter D. H. (1991) Detection of deletions and cryptic translocations in Miller-Diecker syndrome by in situ hybridization. Am. J. Hum. Genet. 49, 707–714.
Overhauser J., Bengtsson U., McMahon J., et al. (1989) Prenatal diagnosis and carrier detection of a cryptic translocation by using DNA markers from the short arm of chromosome 5. Am. J. Hum. Genet. 45, 296–303.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Humana Press Inc.
About this protocol
Cite this protocol
Colleaux, L., Heuertz, S., Molinari, F., Rio, M. (2002). Fluorescence Genotyping for Screening Cryptic Telomeric Rearrangements. In: Fan, YS. (eds) Molecular Cytogenetics. Methods in Molecular Biology™, vol 204. Humana Press. https://doi.org/10.1385/1-59259-300-3:181
Download citation
DOI: https://doi.org/10.1385/1-59259-300-3:181
Publisher Name: Humana Press
Print ISBN: 978-1-58829-006-9
Online ISBN: 978-1-59259-300-2
eBook Packages: Springer Protocols