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Applications of Cytogenetic and Fragile X Molecular Testing in Individuals with Mental Retardation

Year 2007, Volume: 12 Issue: 4, 269 - 272, 01.08.2007

Ülkü Özbey Hüseyin Yüce Murat Kara

Abstract

Objectives: The fragile X syndrome (FXS) is the most frequent cause of inherited mental retardation (MR). It is caused by the progressive expansion of (CGG)n trinucleotide repeats located in the promoter region of the (Fragile X mental retardation 1 gene) FMR1 gene at Xq27.3. The aim of the study is to estimate the prevalance of the FXS and other chromosomal aberrations by cytogenetic and molecular analysis in patients with MR and language disorders. Material and Method: 72 cases with MR who were sent to our laboratory for molecular and cytogenetic search in term of fragile X. The lymphocyte culture was carried out according to standard methods. DNA extraction was done using whole blood DNA extraction kit (Bangalore Genei, Bangalore). This was followed by bisulphite treatment and PCR amplification. Results: Chromosome abnormality was found in 12 cases (16.7%). 7 cases (9.7%) were detected fragile X positive in molecular analysis. The mutations were detected such a full mutation and abnormal methylation in (4.1%) and a premutation carrier (5.5%). We concluded that chromosomal studies in mentally retarded patients help in accurate diagnosis and proper prognosis followed by genetic counseling and management rehabilitation. Conclusion: Due to recent molecular advances, our understanding of the perplexing genetic issues surrounding fragile X syndrome has grown and diagnostic techniques have become both reliable and readily available. ©2007, Fırat University, Medical Faculty

Keywords

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References

  • Incorpora G, Sorge G, Sorge A, Pavone L. Epilepsy in fragile X syndrome. Brain and Development 2002; 24: 766-796.
  • Levitas A. Fragile X syndrome. J Am Acad Child Adolesc Psychiatry 2000; 39: 398-399.
  • Pandey UB, Phadke SR, Mittal B. Molecular diagnosis and genetic counseling for fragile X mental retardation. Neurol India 2004; 52: 36-42.
  • Munir F, Cornish KM, Wilding J. A neuropsychological profile of attention deficits in young males with fragile X syndrome. Neuropsychologia 2000; 38: 1261-1270.
  • Schonberg SA, Packman S. X-linked mental retardation. Rudolp AM, Hoffman Julien IE, Rudolp CD (editors). Rudolph’s Pediatrics. 20th edition, Stamford. Appleton & Lange: 1996. p.426-427.
  • Ozbey U, Yüce H, Kara M, Kabakuş N, Elyas H. Cytogenetic Analysis in Children with Mental Retarded in Elazig Region. Fırat University Journal of Health Sciences 2006; 20: 45-48.
  • Bolton P, Holland A. Chromosomal abnormalities. In: Rutter M, Taylır E, Hersov L, editors. Child and Adolescent Psychiatry, Modern Approaches. 3rd ed. Oxford: Blackwell Science: 1994. p.152-71.
  • Flint J, Yule W. Behavioral phenotypes. 2002. In: Rutter M, Taylor E, Hersov L, editors. Child and Adolescent Psychiatry, Modern Approaches. 3rd ed.Oxford: Blackwell Science: 1994. p.666-87
  • Panagopoulos I, Lassen C, Kristoffersson U, Aman P. Methylation PCR approach for detection of fragile X syndrome. Hum Mutat 1999; 14: 71-79.
  • Mark HF, Bier JA, Scola P. The frequency of chromosomal abnormalities in patients referred for fragile X analysis.Ann Clin Lab Sci 1996; 26: 323-328.
  • Nielsen KB, Tommerup N, Poulsen H, Mikkelsen M. X-linked mental retardation with fragile X. A pedigree showing transmission by apparently unaffected males and partial expression in female carriers. Hum Genet 1981; 59: 23-25.
  • Sherman SL, Morton NE, Jacobs PA, Turner G. The marker (X) syndrome: a cytogenetic and genetic analysis. Ann Hum Genet 1984; 48: 21-37.
  • Demirhan O, Tastemir D, Diler RS, Firat S, Avci A. A cytogenetic study in 120 Turkish children with intellectual disability and characteristics of fragile X syndrome.Yonsei Med J 2003; 44: 583- 592.
  • Mulley JC, Sutherland GR. Diagnosis of fragile X syndrome. Fetal Matern Med Rev 1994; 6: 1-15.
  • Baskaran S, Naseerullah MK, Manjunatha KR, et al. Triplet repeat polymorphism and fragile X syndrome in the Indian context. Indian J Med Res 1998; 107: 29-36.
  • Sharma D, Gupta M, Thelma BK. Expansion mutation frequency and CGG/GCC repeat polymorphism in FMR1 and FMR2 genes in an Indian population. Genet Epidemiol 2001; 20: 129-144.
  • Ng Isl, et al. Robust fragile X (CGG)n genotype classification using a methylation specific triple PCR assay. J Med Genet 2004;41:e45.(http://www.jmedaenet.com/cgi/content/full/41/4 /e45).
  • Weinhausel A, Haas OA. Evaluation of the fragile X (FRAXA) syndrome with methylation-sensitive PCR. Hum Genet 2001; 108: 450-458.
  • Kabul Tarihi: 09.04.2007

Mental Retardasyonlu Bireylerde Sitogenetik ve Frajil X Moleküler Testlerin Uygulanması

Year 2007, Volume: 12 Issue: 4, 269 - 272, 01.08.2007

Ülkü Özbey Hüseyin Yüce Murat Kara

Abstract

Amaç: Kalıtsal mental retardasyonun (MR) en yaygın sebebi Frajil X Sendromu'dur (FXS). Xq27.3'deki (Frajil X mental retardasyon 1) FMR-1 geninin promotor bölgesinde yer alan (CGG)n üçlü nükleotid tekrar sayısının artmasıyla bu bozukluk meydana gelmektedir. Bu çalışmanın amacı, MR ve konuşma güçlüğü bozukluğu olan vakalarda, sitogenetik ve moleküler analizlerle diğer kromozomal anormallikler ve FXS'unun insidansını ortaya koymaktır. Gereç ve Yöntem: Laboratuarımıza Frajil-X açısından sitogenetik ve moleküler araştırma için yollanan MR'lu 72 olgu çalışıldı. Lenfosit kültürü standart metodlara göre yapıldı. DNA ekstraksiyonu, tüm kandan DNA ekstraksiyon kit (Bangalore Genei, Bangalore) kullanılarak yapıldı. Bunu bi sülfitle muamele ve (polimeraz zincir reaksiyonu) PZR amplifikasyonu izledi. Bulgular: 12 olguda (%16.7) kromozomal anomali bulundu. 7 olguda (%9.7) moleküler analizde frajil X pozitif olduğu tespit edildi. %4.1'inde tam mutasyon ve anormal metilasyon ve %5.5'inde premutasyon taşıyıcısı olduğu saptandı. Mental geriliğe sahip hastalarda genetik danışma ve yönetim rehabilitasyonu tarafından yapılan kromozomal çalışmaların doğru tanı ve düzenli prognoza yardımcı olduğu sonucuna vardık. Sonuç: Son zamanlardaki moleküler ilerlemelere bağlı olarak, frajil X sendromunu da kapsayan zihni karıştırıcı genetik konularını daha kolay anlamaktayız. Böylece diagnostik teknikler hem güvenilir hem de kolay ulaşılabilir hale gelmiştir. ©2007, Fırat Üniversitesi, Tıp Fakültesi

Keywords

Mental Gerilik Fragile X Sendromu Tam Mutasyon FMR1 Gen Kromozomal Anormallik

References

  • Incorpora G, Sorge G, Sorge A, Pavone L. Epilepsy in fragile X syndrome. Brain and Development 2002; 24: 766-796.
  • Levitas A. Fragile X syndrome. J Am Acad Child Adolesc Psychiatry 2000; 39: 398-399.
  • Pandey UB, Phadke SR, Mittal B. Molecular diagnosis and genetic counseling for fragile X mental retardation. Neurol India 2004; 52: 36-42.
  • Munir F, Cornish KM, Wilding J. A neuropsychological profile of attention deficits in young males with fragile X syndrome. Neuropsychologia 2000; 38: 1261-1270.
  • Schonberg SA, Packman S. X-linked mental retardation. Rudolp AM, Hoffman Julien IE, Rudolp CD (editors). Rudolph’s Pediatrics. 20th edition, Stamford. Appleton & Lange: 1996. p.426-427.
  • Ozbey U, Yüce H, Kara M, Kabakuş N, Elyas H. Cytogenetic Analysis in Children with Mental Retarded in Elazig Region. Fırat University Journal of Health Sciences 2006; 20: 45-48.
  • Bolton P, Holland A. Chromosomal abnormalities. In: Rutter M, Taylır E, Hersov L, editors. Child and Adolescent Psychiatry, Modern Approaches. 3rd ed. Oxford: Blackwell Science: 1994. p.152-71.
  • Flint J, Yule W. Behavioral phenotypes. 2002. In: Rutter M, Taylor E, Hersov L, editors. Child and Adolescent Psychiatry, Modern Approaches. 3rd ed.Oxford: Blackwell Science: 1994. p.666-87
  • Panagopoulos I, Lassen C, Kristoffersson U, Aman P. Methylation PCR approach for detection of fragile X syndrome. Hum Mutat 1999; 14: 71-79.
  • Mark HF, Bier JA, Scola P. The frequency of chromosomal abnormalities in patients referred for fragile X analysis.Ann Clin Lab Sci 1996; 26: 323-328.
  • Nielsen KB, Tommerup N, Poulsen H, Mikkelsen M. X-linked mental retardation with fragile X. A pedigree showing transmission by apparently unaffected males and partial expression in female carriers. Hum Genet 1981; 59: 23-25.
  • Sherman SL, Morton NE, Jacobs PA, Turner G. The marker (X) syndrome: a cytogenetic and genetic analysis. Ann Hum Genet 1984; 48: 21-37.
  • Demirhan O, Tastemir D, Diler RS, Firat S, Avci A. A cytogenetic study in 120 Turkish children with intellectual disability and characteristics of fragile X syndrome.Yonsei Med J 2003; 44: 583- 592.
  • Mulley JC, Sutherland GR. Diagnosis of fragile X syndrome. Fetal Matern Med Rev 1994; 6: 1-15.
  • Baskaran S, Naseerullah MK, Manjunatha KR, et al. Triplet repeat polymorphism and fragile X syndrome in the Indian context. Indian J Med Res 1998; 107: 29-36.
  • Sharma D, Gupta M, Thelma BK. Expansion mutation frequency and CGG/GCC repeat polymorphism in FMR1 and FMR2 genes in an Indian population. Genet Epidemiol 2001; 20: 129-144.
  • Ng Isl, et al. Robust fragile X (CGG)n genotype classification using a methylation specific triple PCR assay. J Med Genet 2004;41:e45.(http://www.jmedaenet.com/cgi/content/full/41/4 /e45).
  • Weinhausel A, Haas OA. Evaluation of the fragile X (FRAXA) syndrome with methylation-sensitive PCR. Hum Genet 2001; 108: 450-458.
  • Kabul Tarihi: 09.04.2007
There are 19 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Ülkü Özbey This is me

Hüseyin Yüce This is me

Murat Kara This is me

Publication Date August 1, 2007
Published in Issue Year 2007 Volume: 12 Issue: 4

Cite

APA Özbey, Ü., Yüce, H., & Kara, M. (2007). Mental Retardasyonlu Bireylerde Sitogenetik ve Frajil X Moleküler Testlerin Uygulanması. Fırat Tıp Dergisi, 12(4), 269-272.
AMA Özbey Ü, Yüce H, Kara M. Mental Retardasyonlu Bireylerde Sitogenetik ve Frajil X Moleküler Testlerin Uygulanması. Fırat Tıp Dergisi. August 2007;12(4):269-272.
Chicago Özbey, Ülkü, Hüseyin Yüce, and Murat Kara. “Mental Retardasyonlu Bireylerde Sitogenetik Ve Frajil X Moleküler Testlerin Uygulanması”. Fırat Tıp Dergisi 12, no. 4 (August 2007): 269-72.
EndNote Özbey Ü, Yüce H, Kara M (August 1, 2007) Mental Retardasyonlu Bireylerde Sitogenetik ve Frajil X Moleküler Testlerin Uygulanması. Fırat Tıp Dergisi 12 4 269–272.
IEEE Ü. Özbey, H. Yüce, and M. Kara, “Mental Retardasyonlu Bireylerde Sitogenetik ve Frajil X Moleküler Testlerin Uygulanması”, Fırat Tıp Dergisi, vol. 12, no. 4, pp. 269–272, 2007.
ISNAD Özbey, Ülkü et al. “Mental Retardasyonlu Bireylerde Sitogenetik Ve Frajil X Moleküler Testlerin Uygulanması”. Fırat Tıp Dergisi 12/4 (August 2007), 269-272.
JAMA Özbey Ü, Yüce H, Kara M. Mental Retardasyonlu Bireylerde Sitogenetik ve Frajil X Moleküler Testlerin Uygulanması. Fırat Tıp Dergisi. 2007;12:269–272.
MLA Özbey, Ülkü et al. “Mental Retardasyonlu Bireylerde Sitogenetik Ve Frajil X Moleküler Testlerin Uygulanması”. Fırat Tıp Dergisi, vol. 12, no. 4, 2007, pp. 269-72.
Vancouver Özbey Ü, Yüce H, Kara M. Mental Retardasyonlu Bireylerde Sitogenetik ve Frajil X Moleküler Testlerin Uygulanması. Fırat Tıp Dergisi. 2007;12(4):269-72.