Molecular studies in children with fragile X syndrome
DOI:
https://doi.org/10.18203/2320-6012.ijrms20174556Keywords:
CGG repeats, Fragile X syndrome, Fragile site, Learning disability, PCR analysisAbstract
Background: Fragile X Syndrome (FXS) is the most common single gene cause of Learning (intellectual) Disability (LD). FMR1 gene mutation is the commonest cause for this syndrome. The present study aims to analyze the incidence of the syndrome in Kerala population.
Methods: Study was conducted among 86 children belonging to different places of Kerala. Children were selected on the basis of IQ scores and typical features of FXS. Blood samples were taken and routine karyotype was performed. PCR analyses were also conducted.
Results: Majority of the children showed typical features of FXS. Out of 86 samples, six showed chromosomal aberrations were excluded. PCR analyses in 55 samples, screened 35 samples with FMR1 mutation, in which 26 samples having pre- mutation and 9 samples with full mutation.
Conclusions: Through this genetic study, differential diagnosis of LD children with FXS, LD children with constitutional chromosome abnormalities, and LD children without any apparent genetic abnormalities could be established.
References
Fryns JP. X-linked mental retardation and the Fragile X syndrome, A clinical approach in Davies KE (ed)The fragile X syndrome. Oxford University Press, Oxford; 1988:1-39.
Hagerman RJ. Physical and behavioural phenotype. In: Hagerman RJ, Cronister A, editors. Fragile-X syndrome: diagnosis, treatment and research. Baltimore: The Johns Hopkins University Press; 1996.
Lubs HA. A marker X chromosome. Am J Hum Genet. 1969;21:231-44.
Kremer EJ, Pritchard M, Lynch M, Yu S, Holman K, Baker E, et al. Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p (CGG), Science. 1991;252:1711-4.
Verkerk A, Pieretti M, Sutcliffe J, Fu Y, Kuhl D, Pizzuti A, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in Fragile X syndrome. Cell. 1991;65:905-14.
Madhumita CR, Kabra M, Sharma D, Singh D, Thelma AD. Prevalence and phenotype consequence of FRAXA and FRAXE alleles in a large ethnically diverse. Ind J Hum Gene. 2006;12(1):17-22.
Arakaki DT, Sparkes RS. Mitotechnique for culturing leukocytes from whole blood. Basel. 1963;60:2-7.
Manjunatha KR, Rao BSS, Narayanan HS, Girimaji SR, Shobha S, Gandhi DH et al. Fragile X syndrome: The first case report from India. Genome. 1988;30(Suppl):205.
Seabright M. A rapid banding technique for Human chromosomes. Lancet II: 1971;971-2.
Sambrook J, Fritsch EF, Maniatis T. Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbor Laboratory, Cold Spring Harbor; 1989.
Blomquist HK, Gustavson KH, Holmgren G, Nordenson I and Palsson-Strae U Fragile Xsyndrome in mildly mentally retarded children in a Northern Swedish county. A prevalencestudy. Clin Genet. 1983;24:393-8.
de Vries BB, Wiegers AM, Smits AP, Mohkamsing S, Duivenvoorden HJ, Fryns JP, et al. Mental status of females with an FMR1 gene full mutation. Am J Hum Genet’. 1996;58:1025-32.
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;20:129-44.
Gustavson KH, Dahlbom K, Flood A Effect of folic acid treatment in the fragile X syndrome. Clin Genet. 1986;27:463-7.
Shin SK, Yoo HW. Etiological Classification of Mentally Retarded Children Enrolled in a Special Educational Institution. J Korean Pediatr Soc. 1994; 37:1437-48.
Hong KM, Kim JH, Moon SY, Oh SK. Chromosomal abnormalities in child psychiatric patients. J Korean Med Sci. 1999;14:377-85.
Strelnikov V, Zemlyakova V, Artamonov E and Vasil'ev E. Methylation-sensitive multiplex FRAXA-FRAXE PCR assay is a powerful non-invasive neonatal screening method capable of detecting genetic abnormalities in newborn boys. (2000). Institute of Molecular Medicine, Moscow Medical Academy, Moscow.
Wang Q, Green E, Bobrow M, Mathew CG. Rapid non radioactive screening test for fragile x mutation at the fraxa and fraxe loci Journal of medical genet. 1995;32(3):170-3.
Turner G, Webb T, Wake S. Prevalence of fragile X syndrome. Am J Med Genet. 1996;64:16-97.
Pieretti M, Zhang F, Fu Y, Warren S, Oostra B, Caskey C, et al. Absence of expression of the FMR-1 gene in fragile X syndrome. Cell. 1991;66:817-22.
Sutcliffe J, Nelson D, Zhang F, Pieretti M, Caskey C, Saxe D, et al. DNA methylation represses FMR-1 transcription in fragile X syndrome. Hum Mol Genet. 1992;1:397-400.
Xuncla M, Fragile X syndrome prenatal diagnosis: parental attitudes and reproductive responses. Reprod Biomed Online. 2010;21(4):560-5.
Filipovic-Sadic S, A novel FMR1 PCR method for the routine detection of low abundance expanded alleles and full mutations in fragile X syndrome. Clin Chem. 2010;56(3):399-408.
Hantash FM. Fragile X syndrome: is now the time for population screening? MLO Med Lab Obs. 2010;42(5):20-2.
Jacquemont S, Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci Transl Med. 2011;3(64):64ra61.
Tassone F, Newborn screening in fragile X syndrome: prevalence and allele distribution of the FMR1 gene. Paper presented at: American College of Medical Genetics Annual Clinical Genetics meeting; July 26, 2012; Charlotte, North Carolina, USA. Availabe form http://www.fragilex.org/community/internationalfragile-x-conference/miami 2012/agenda/. Accessed October 19, 2012.
Chetan GK, Manjunatha KR, Arathi R, Latha P. Genetics of Fragile-X syndrome: A systematic data from the Indian population. Int J Hum Gent. 2002;2:69-72.
Karmasagar A, Pandit L, Kumar S and Karunasagar I. Department of Neurology, KS Hegde Medical Academy and Department of Fishery Microbiology University of Agricultural Sciences, Mangalore, India Ind J Med Res. 2005;122:429-33.
Fernandez-Carvajal I, Walichiewicz P, Xiaosen X, Pan R, Hagerman PJ, Tassone F. Screening for expanded alleles of the FMR1 gene in blood spots from newborn males in a Spanish population. The Journal of Molecular Diagnostics. 2009;11(4):324-9.
Reiss AL, Kazazian H, Krebs C, McAughan A, Boehm C, Abrams M, et al. Frequency and stability of the fragile X premutation. Hum Mol Genet. 1994;3:393-398.
Pembrey ME, Anionwu EN. Ethical aspects of genetic screening and diagnosis. In: Rimoin DL, Connor JM, Pyeritz RE, editors. Emery and Rimoin’s principles and practice of medical genetics. 3rd ed. New York: Churchill Livingstone. 1996;641-53
Hagerman RJ, Berry-Kravis E, Kaufmann WE, Ono MY, Tartaglia N, Lachiewicz A, et al. Advances in the treatment of fragile X syndrome. Pediatrics. 2009;123:378-90.
Utari A, Adams E, Berry-Kravis E, Chavez A, Scaggs F, Ngotran L, et al. Aging in the fragile X syndrome. J Neurodev Disord. 2010;2:70-6.
