Skip to main content
SpringerLink
Log in

Subtelomeric rearrangements in idiopathic mental retardation

  • Original Article
  • Published:
The Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Objective : To estimate the frequency of subtelomeric rearrangements in patients with sporadic and non-syndromic idiopathic mental retardation (IMR).Methods: A total of 18 IMR patients were taken for the study. Selection criteria included no known syndromes or chromosomes abnormalities and known causes of IMR. All patients signed an informed consent to participate. Chromosome analysis was carried out on all patients to rule out gross chromosome abnormalities. Lymphocyte cultures were initiated and harvested using standard protocols. For fluorescencein situ hybridization (FISH), Chromoprobe Multiprobe-T system was used. this system consists of 24 embossed areas with each area having one reversibly bound subtelomere probe for a specific chromosome. the subtelomere probes were differentially labeled with green fluorescence for short arm and orange for the long arm. Hybridization, washing and staining are done using standard protocols. A minimum of 5 metaphases were analyzed per chromosome per patient.Results : A total of 2 subtelomeric rearrangements were detected (11.1%). Case 1 involved a 17-year-old with severe MR, profound deafness and dysmorphic features with reciprocal translocation t(3;7)(q26.2; p15.1). the second case involved a 4.6-year-old with mild developmental delay and a terminal deletion of the long arm of chromosome 2, del(2) (q37.3). the frequency of abnormalities detected in our study is in agreement with published reports.Conclusion : Subtelomeric screening with FISH is a useful tool for investigation of IMR, however, it is not cost effective in all cases. Conventional chromosome analysis coupled with targeted FISH testing might be the optimal strategy for investigation of IMR.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Joyce CA, Dennis NR, Cooper S, Brown CE. Subtelomeric rearrangements: results from a study of selected and unselected probands with idiopathic mental retardation and control individuals by using high-resolution G-banding and FISH.Hum Genet 2001; 109: 440–451.

    Article  PubMed  CAS  Google Scholar 

  2. Brown WR, Mackinnon PJ, Villasante A, Spurr N, Buckle VJ, Dobson MJ. Structure and polymorphism of human telomereassociated DNA.Cell 1990; 63: 119–132.

    Article  PubMed  CAS  Google Scholar 

  3. Wilkie AOM, Higgs DR, Rack KA, Buckle VJ, Spurr NK, Fischel-Ghodsian N, Ceccherini I, Brown WR, Harris PC. Stable length polymorphism of up to 260 kb at the tip of the short arm of chromosome 16. Cell 1991; 64: 595–606.

    Article  PubMed  CAS  Google Scholar 

  4. Youngman S, Bates GP, Williams S, McClatchey AI, Baxendale S, Sedlacek Z, Altherr M, Wasmuth JJ, Macdonald ME, Gusella JF, Sheer D, Lehrach H. the telomeric 60 kb of chromosome 4p is homologous to telomeric regions on 13p, 15p, 21p, and 22p.Genomics 1992; 14: 350–356.

    Article  PubMed  CAS  Google Scholar 

  5. Flint J, Rochette J, Craddock CF, Dode C, Vignes B, Horsley SW, Kearney L, Buckle VJ, Ayyub H, Higgs DR. Chromosomal stabilization by a subtelomeric rearrangement involving two closely related Alu elements.Hum Mol Genet 1996; 5: 1163–1169.

    Article  PubMed  CAS  Google Scholar 

  6. Flint J, Bates GP, Clark K, Dorman A, Willingham D, Roe BA, Micklem G, Higgs DR, Louis EJ. Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains.Hum Mol Genet 1997; 6: 1305–1313.

    Article  PubMed  CAS  Google Scholar 

  7. Kermouni A, Van Roost E, Arden KC, Vermeesch JR, Weiss S, Godelaine D, Flint J, Lurquin C, Szikora JP, Higgs DR. the IL-9 receptor gene (IL9R): genomic structure, chromosomal localization in the pseudoautosomal region of the long arm of the sex chromosomes, and identification of IL9R pseudogenes at 9qter, 10 pter, 16 pter and 18pter.Genomics 1995; 29: 371–382.

    Article  PubMed  CAS  Google Scholar 

  8. Rouquier S, Taviaux S, Trask BJ, Brand-Arpon V, Vandenengh G, Demaille J, Giorgi D. Distribution of olfactory receptor genes in the human genome.Nat Genet 1998; 18: 243–250.

    Article  PubMed  CAS  Google Scholar 

  9. Blouin J-L, Christie DH, Gos A, Lynn A, Morris MA, Ledbetter DH, Chakravarti A, Antonarakis SE. A new dinucleotide repeat polymorphism at the telomere of chromosome 21q reveals a significant difference between male and female rates of recombination.Am J Hum Genet 1995; 57: 388–394.

    PubMed  CAS  Google Scholar 

  10. Laurie DA, Hulten MA. Further studies on bivalent chiasma frequency in human males with normal karyotypes.Ann Hum Genet 1985; 49: 189–201.

    Article  PubMed  CAS  Google Scholar 

  11. Flint J, Wilkie AO, Buckle VJ, Winter RM, Holland AJ, McDermid HE. the detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation.Nat Genet 1995; 9: 132–140.

    Article  PubMed  CAS  Google Scholar 

  12. Hoovers JM, Bijlsma EK, Sluijter S, Hennekam RCM. Subtelomeric rearrangements as a cause for mental retardation.Eur J Hum Genet 1998; 6: 41–42.

    Google Scholar 

  13. Viot G, Gosset P, Fert S, Prieur M, Turleau C, Raoul O, De Blois MC, Lyonnet S, Munnich A, Vekemans M. Cryptic subtelomeric rearrangements detected by FISH in mentally retarted and dysmorphic patients.Am J Hum Genet 1998; 63: A44.

    Google Scholar 

  14. Vorsanova SG, Yurov YB, Demidova IA, Kolotii AD, Soloviev IV. FISH analysis of microaberrations near telomeric chromosomal regions in children with mental retardation.Am J Med Genet 1998; 96: A345.

    Google Scholar 

  15. Knight SJL, Regan R, Nicod A, Horsley SW, Kearney L, Homfray T, Winter RM, Bolton P, Flynt J. Subtle chromosomal rearrangements in children with unexplained mental retardation.Lancet 1999; 354: 1676–1681.

    Article  PubMed  CAS  Google Scholar 

  16. Lamb AN, Lytle CH, Aylsworth AS, Powel CM, Rao KW, Hendrickson M, Carey JC, Opitz JM, Viskochil DH, Leonard CO, Brothman AR, Stephan M, Bartley JA, Hackbarth M, McCarthy D, Proffitt J. Low proportion of subtelomeric rearrangements in a population of patients with mental retardation and dysmorphic features.Am J Hum Genet 1999; 65: A924.

    Article  Google Scholar 

  17. Slavotinek A, Rosenberg M, Knight S, Gaunt L, Fergusson W, Killoran C, Clayton-Smith J, Kingston H, Campbell RHA, Flint J, Donnai D, Biesecker L. Screening for submicroscopic chromosome rearrangements in children with idiopathic mental retardation using microsatellite markers for the chromosome telomeres.J Med Genet 1999; 36: 405–411.

    PubMed  CAS  Google Scholar 

  18. Colleaux L, Rio M, Heuertz S, Moindrault S, Turleau C, Ozilou C, Gosset P, Raoult O, Lyonnet S, Cormier-Daire V, Amiel J, Le Merrer M, Picq M, de Blois MC, Prieur M, Romana S, Cornelis F, Vekemans M, Munnich A. A novel automated strategy for screening cryptic telomeric rearrangements in children with idiopathic mental retardation.Eur J Hum Genet 2001; 9: 319–327.

    Article  PubMed  CAS  Google Scholar 

  19. Kirchhoff M, Rose H, Lundsteen C. High resolution comparative genomic hybridization in clinical cytogenetics.J Med Genet 2001; 38: 740–744.

    Article  PubMed  CAS  Google Scholar 

  20. Riegel M, Baumer A, Jamar M, Delbecque K, Herens C, Verloes A, Schinzel A. Submicroscopic terminal deletions and duplications in retarded patients with unclassified malformation syndromes.Hum Genet 2001; 109: 286–294.

    Article  PubMed  CAS  Google Scholar 

  21. Rosenberg MJ, Killoran C, Dziadzio L, Chang S, Stone DL, Meek J, Aughton D, Bird LM, Bodurtha J, Cassidy SB, Graham JM Jr., Grix A, Guttmarcher AE, Hudgins L, Kozma C, Michaelis RC, Pauli R, Peters KF, Rosenbaum KN, Tifft CJ, Wargowski D, Williams MS, Biesecker LG. Scanning for telomeric deletions and duplications and uniparental disomy using genetic markers in 120 children with malformations.Hum Genet 2001; 109: 311–318.

    Article  PubMed  CAS  Google Scholar 

  22. Rossi E, Piccini F, Zollino M, Neri G, Caselli D, Tenconi R, Castellan C, Carrozzo R, Danesino C, Zuffardi O, Ragusa A, Castiglia L, Galesi O, Greco D, Romano C, Pierluigi M, Perfume C, Di Rocco M, Faravelli F, Dagna BF, Bonaglia M, Bedeschi M, Borgatti R. Cryptic telomeric rearrangements in subjects with mental retardation associated with dysmorphism and congenital malformations.J Med Genet 2001; 38: 417–420.

    Article  PubMed  CAS  Google Scholar 

  23. Anderlid B-M, Schoumans J, Anneren G, Sahlen S, Kyllerman M, Vujic M, Hagberg B, Blennow E, Nordenskjold M. Subtelomeric rearrangements detected in patients with idiopathic mental retardation.Am J Med Genet 2002; 107: 275–284.

    Article  PubMed  Google Scholar 

  24. Baker E, Hinton L, Callen DF, Altree M, Dobbie A, Eyre HJ, Sutherland GR, Thompson E, Thompson P, Woollatt E, Haan E. Study of 250 children with idiopathic mental retardation reveals nine cryptic and diverse subtelomeric chromosome anomalies.Am J Med Genet 2002; 107: 285–293.

    Article  PubMed  Google Scholar 

  25. Clarkson B, Pavenski K, Dupuis L, Kennedy S, Meyn S, Nezrati MM, Nie G, Weksberg R, Withers S, Quercia N, Teebi AS, Teshima I. Detecting rearrangements in children using subtelomeric FISH and SKY.Am J Med Genet 2002; 107: 267–274.

    Article  PubMed  Google Scholar 

  26. van Karnebeek CDM, Koevoets C, Sluijter S, Bijlsma EK, Smeets DFMC, Redeker EJ, Hennekam RCM, Hoovers JMN. Prospective screening for subtelomeric rearrangements in children with mental retardation of unknown aetiology: the Amsterdam experience.J Med Genet 2002; 39: 546–553.

    Article  PubMed  Google Scholar 

  27. Tonk VS, Wyandt HE, Huang X, Patel N, Morgan DL, Kukolich M, Lockhart LH, Velgaleti GVN. Disease associated balanced chromosome rearrangements (DBCR): report of two new cases.Ann Genet 2003; 46: 37–43.

    PubMed  CAS  Google Scholar 

  28. Jalal SM, Harwood AR, Sekhon GS, Lorentz CP, Ketterling RP, Babovic-Vuksanovic D, Meyer RG, Ensenauer R, Anderson MH, Michels VV. Utility of subtelomeric fluorescent DNA probes for detection of chromosome anomalies in 425 patients. Genet Med 2003; 5: 28–34.

    PubMed  CAS  Google Scholar 

  29. Barber JCK, Joyce CA, Collinson MN, Nicholson JC, Willatt LR, Dyson HM, Bateman MS, Green AJ, Yates JRW, Dennis NR. Duplication of 8p23.1: a cytogenetic anomaly with no established clinical significance.J Med Genet 1998; 35: 491–496.

    Article  PubMed  CAS  Google Scholar 

  30. Barber JCK, Reed CJ, Dahoun SP, Joyce CA. Amplification of a pseudogene cassette underlies euchromatic variation of 16p at the cytogenetic level.Hum Genet 1999;104: 211–218.

    Article  PubMed  CAS  Google Scholar 

  31. Gardner RJM, Sutherland GR. Chromosome abnormalities and genetic counseling. Oxford University Press, Oxford. 1996.

    Google Scholar 

  32. Harwood A, Anderson M, Jalal SM. Technical comparison of two commercially available telomere specific probe set.J Assoc Genet Tech 2001; 27: 132–134.

    Google Scholar 

  33. Jalal SM, Harwood AR, Anderson MH, Sekhon GS, Ketterling RP, Michels W. Analysis by telomere specific FISH probes of 191 karyotypically normal patients with nonspecific dysmorphic features or developmental delay, or history of multiple miscarriages.Am J Hum Genet 2001; 69: 333.

    Google Scholar 

  34. Fan Y-S, Zhang Y, Speevak M, Farrell S, Jung JH, Siu VM. Detection of submicroscopic aberrations in patients with unexplained mental retardation by fluorescence in situ hybridization using multiple subtelomeric probes.Genet Med 2001; 3: 416–421.

    PubMed  CAS  Google Scholar 

  35. Macina RA, Negorev DG, Spais C, Ruthig LA, Hu X-L, Riethman HC. Sequence organization of the human chromosome 2q telomere.Hum Mol Genet 1994; 3: 1847–1853.

    Article  PubMed  CAS  Google Scholar 

  36. Wolff DJ, Clifton K, Karr C, Charles J. Pilot assessment of the subtelomeric regions of children with autism: Detection of a 2q deletion.Genet Med 2002; 4: 10–14.

    Article  PubMed  Google Scholar 

  37. Buxbaum JD, Silverman JM, Smith CJ, Kilifarski M, Reichert J, Hollander E, Lawlor BA, Fitzgerald M, Greenberg DA, Davis KL. Evidence for a susceptibility gene for autism on chromosome 2 and for genetic heterogeneity.Am J Hum Genet 2001; 68: 1514–1520.

    Article  PubMed  CAS  Google Scholar 

  38. de Vries BB, White SM, Knight SJ, Regan R, Homfray T, Young ID, Super M, McKeown, Splitt M, Quarrell OWJ, Trainer AH, Niermeijer MF, Malcolm S, Flint J, Hurst JA, Winter RM. Clinical studies on submicroscopic subtelomeric rearrangements: a check list.J Med Genet 2001; 38: 145–150.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA

    Gopalrao V. N. Velagaleti, Sally S. Robinson, Bobby M. Rouse & Lillian H. Lockhart

  2. Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA

    Gopalrao V. N. Velagaleti

  3. Department of Pediatrics, Texas Tech Health Sciences Center, Lubbock, TX, USA

    Vijay S. Tonk

Authors
  1. Gopalrao V. N. Velagaleti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sally S. Robinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bobby M. Rouse
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vijay S. Tonk
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lillian H. Lockhart
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gopalrao V. N. Velagaleti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Velagaleti, G.V.N., Robinson, S.S., Rouse, B.M. et al. Subtelomeric rearrangements in idiopathic mental retardation. Indian J Pediatr 72, 679–685 (2005). https://doi.org/10.1007/BF02724077

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02724077

Key words

Search

Navigation