Skip to main content

Advertisement

SpringerLink
Log in

Macrocephalic mental retardation associated with a novel C-terminal MECP2 frameshift deletion

  • Original Paper
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

We report a novel C-terminal MECP2 frameshift deletion (1135_1142delCCCGTG CC) in a 19-year-old woman with mental retardation and epilepsy. Preservation of language capabilities, purposeful hand use and sufficient locomotion implied an atypical variant of Rett syndrome (OMIM 312750). Occipito-frontal head circumference was large at birth (36 cm; SDS 1.7) and increased until adulthood (58.5 cm; SDS 2.3). Conclusion: Our observation indicates that head size and head growth are of limited reliability in the diagnosis of MECP2-associated phenotypes.

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

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

MeCP2 :

methyl-CpG-binding protein 2

RTT :

Rett syndrome

References

  1. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23: 185–188

    Article  CAS  PubMed  Google Scholar 

  2. Cheadle JP, Gill H, Fleming N, Maynard J, Kerr A, Leonard H, Krawczak M, Cooper DN, Lynch S, Thomas N, Hughes H, Hulten M, Ravine D, Sampson JR, Clarke A (2000) Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location. Hum Mol Genet 9: 1119–1129

    Article  CAS  PubMed  Google Scholar 

  3. Flügel B, Greil H, Sommer K (1986) Anthropologischer Atlas. Verlag Tribüne, Berlin

  4. Hagberg G, Stenbom Y, Engerstrom IW (2001) Head growth in Rett syndrome. Brain Dev 23[Suppl 1]: S227–S229

    Google Scholar 

  5. Huppke P, Held M, Laccone F, Hanefeld F (2003) The spectrum of phenotypes in females with Rett syndrome. Brain Dev 25: 346–351

    Article  PubMed  Google Scholar 

  6. Kammoun F, de Roux N, Boespflug-Tanguy O, Vallee L, Seng R, Tardieu M, Landrieu P (2004) Screening of MECP2 coding sequence in patients with phenotypes of decreasing likelihood for Rett syndrome: a cohort of 171 cases. J Med Genet 41: e85

    Google Scholar 

  7. Klauck SM, Lindsay S, Beyer KS, Splitt M, Burn J, Poustka A (2002) A mutation hot spot for nonspecific X-linked mental retardation in the MECP2 gene causes the PPM-X syndrome. Am J Hum Genet 70: 1034–1037

    Article  CAS  PubMed  Google Scholar 

  8. Mnatzakanian GN, Lohi H, Munteanu I, Alfred SE, Yamada T, MacLeod PJ, Jones JR, Scherer SW, Schanen NC, Friez MJ, Vincent JB, Minassian BA (2004) A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome. Nat Genet 36: 339–341

    Article  CAS  PubMed  Google Scholar 

  9. Nielsen JB, Henriksen KF, Hansen C, Silahtaroglu A, Schwartz M, Tommerup N (2001) MECP2 mutations in Danish patients with Rett syndrome: high frequency of mutations but no consistent correlations with clinical severity or with the X chromosome inactivation pattern. Eur J Hum Genet 9: 178–184

    Article  CAS  PubMed  Google Scholar 

  10. Renieri A, Meloni I, Longo I, Ariani F, Wari F, Pescucci C, Cambi F (2003) Rett syndrome: the complex nature of a monogenic disease. J Mol Med 81: 346–354

    PubMed  Google Scholar 

  11. Roche AF, Mukherjee D, Guo S, Moore WM (1987) Head circumference reference data: birth to 18 years. Pediatrics 79: 706–712

    CAS  PubMed  Google Scholar 

  12. Schanen C, Francke U (1998) A severely affected male born into a Rett syndrome kindred supports X-linked inheritance and allows extension of the exclusion map. Am J Hum Genet 63: 267–269

    Article  CAS  PubMed  Google Scholar 

  13. Wan M, Lee SS, Zhang X, Houwink-Manville I, Song HR, Amir RE, Budden S, Naidu S, Pereira JL, Lo IF, Zoghbi HY, Schanen NC, Francke U (1999) Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots. Am J Hum Genet 65: 1520–1529

    Article  CAS  PubMed  Google Scholar 

  14. Weaving LS, Williamson SL, Bennetts B, Davis M, Ellaway CJ, Leonard H, Thong MK, Delatycki M, Thompson EM, Laing N, Christodoulou J (2003) Effects of MECP2 mutation type, location and X-inactivation in modulating Rett syndrome phenotype. Am J Med Genet 118A: 103–114

    Article  PubMed  Google Scholar 

  15. Yamashita Y, Kondo I, Fukuda T, Morishima R, Kusaga A, Iwanaga R, Matsuishi T (2001) Mutation analysis of the methyl-CpG-binding protein 2 gene (MECP2) in Rett patients with preserved speech. Brain Dev 23[Suppl 1]: S157–S160

  16. Yntema HG, Kleefstra T, Oudakker AR, Romein T, de Vries BB, Nillesen W, Sistermans EA, Brunner HG, Hamel BC, van Bokhoven H (2002) Low frequency of MECP2 mutations in mentally retarded males. Eur J Hum Genet 10: 487–490

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Prof. Dr. Evelin Schröck and Dr. Walter Werner for helpful discussions.

Author information

Authors and Affiliations

  1. Institut für Klinische Genetik, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 , Dresden, Germany

    Konrad Oexle & Sigrid Tinschert

  2. Labor Dr. Reising-Ackermann und Partner, Leipzig, Germany

    Barbara Thamm-Mücke

  3. Epilepsiezentrum Kleinwachau, Liegau-Augustusbad, Germany

    Thomas Mayer

Authors
  1. Konrad Oexle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barbara Thamm-Mücke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Mayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sigrid Tinschert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Konrad Oexle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oexle, K., Thamm-Mücke, B., Mayer, T. et al. Macrocephalic mental retardation associated with a novel C-terminal MECP2 frameshift deletion. Eur J Pediatr 164, 154–157 (2005). https://doi.org/10.1007/s00431-004-1583-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-004-1583-x

Search

Navigation