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2014 | 61 | 2 | 259-263
Article title

Simple molecular diagnostic method for Fragile X syndrome in Egyptian patients: Pilot study

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Background: Poor knowledge about Fragile X syndrome (FXS) may be a major barrier to early diagnosis that could improve quality of life and prognosis especially in the developing countries. Aim: The aim of this study was to evaluate simple and reproducible method for premutation detection in females of fragile X families for the first time in Egypt. Subjects and Methods: We have developed a rapid modified polymerase chain reaction (PCR)-based screening tool for expanded Fragile X mental retardation 1 (FMR1) alleles. This method utilizes betaine as additive to facilitate FMR 1 gene amplification. We screened fifty three males, thirty two first-degree females; twenty normal healthy controls in addition to six reference samples. Results: Simple PCR method showed 16 males with abnormal CGG repeats, where 10 of their mothers and four sisters had FMR 1 premutation. Consanguineous marriage was present in 66.6% percent of the studied families. Studying the correlation between genotype and clinical manifestations showed premature ovarian failure in 40% and learning disability in 50% of the studied female carriers. Conclusion: FXS has to be ruled out in families with consanguineous parents, before assuming that familial mental retardation is due to autosomal recessive gene defects. Early carrier detection may reduce the number of affected children. In conclusion, more studies are still needed of much larger sample size with known allele sizes in order to guarantee the accuracy of the method used.
Physical description
  • Department of Research on Children with Special Needs, National Research Centre, Cairo, Egypt
  • Department of Biochemistry, Faculty of Pharmacy, Cairo, Egypt
  • Department of Research on Children with Special Needs, National Research Centre, Cairo, Egypt
  • Department of Biochemistry, Faculty of Pharmacy, Cairo, Egypt
  • Department of Microbial Biotechnology, National Research Centre, Cairo, Egypt
  • Bilgen T, Keser I, Mihci E, Haspolat S, Tacoy S, Luleci G (2005) Molecular analysis of fragile X syndrome in Antalya Province. Indian J Med Sci 59: 150-155.
  • Brown WT, Nolin S, Houck G Jr, Ding X, Glicksman A, Li SY, Stark-Houck S, Brophy P, Duncan C, Dobkin C, Jenkins E (1996) Prenatal diagnosis and carrier screening for fragile X by PCR. Am J Med Genet 64: 191-195.
  • Coffee B, Keith K, Albizua I, Malone T, Mowrey J, Sherman SL, Warren ST (2009) Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA. Am J Hum Genet 85: 503-514.
  • Fernandez-Carvajal I, Walichiewicz P, Xiaosen X, Pan R, Hagerman PJ, Tassone F (2009) Screening for expanded alleles of the FMR 1 gene in blood spots from newborn males in a Spanish population. J Mol Diagn 11: 324-329.
  • Fu YH, Kuhl DP, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S, Verkerk AJ, Holden JJ, Fenwick RG Jr, Warren ST (1991) Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67: 1047-1058.
  • Goodlin-Jones BL, Tassone F, Gane LW, Hagerman RJ (2004) Autistic spectrum disorder and the fragile X premutation. J Dev Behav Pediatr 25: 392-398.
  • Greco CM, Berman RF, Martin RM, Tassone F, Schwartz PH, Chang A, Trapp BD, Iwahashi C, Brunberg J, Grigsby J, Hessl D, Becker EJ, Papazian J, Leehey MA, Hagerman RJ, Hagerman PJ (2006) Neuropathology of fragile X-associated tremor/ataxia syndrome (FXTAS). Brain 129: 243-255.
  • Hagerman RJ, Amiri K, Cronister A (1991) Fragile X checklist. Am J Med Genet 38: 283-287.
  • Hagerman RJ, Hagerman PJ (2002) The fragile X premutation: into the phenotypic fold. Curr Opin Genet Dev 12: 278-283.
  • Hagerman RJ, Hall DA, Coffey S, Leehey M, Bourgeois J, Gould J, Zhang L, Seritan A, Berry-Kravis E, Olichney J, Miller JW, Fong AL, Carpenter R, Bodine C, Gane LW, Rainin E, Hagerman H, Hagerman PJ (2008) Treatment of fragile X-associated tremor ataxia syndrome (FXTAS) and related neurological problems. Clin Interv Aging 3: 251-262.
  • Hecimovic S, Vlasic J, Barisic L, Markovic D, Culic V, Pavelic K (2001) A simple and rapid analysis of triplet repeat diseases by expand long PCR. Clin Chem Lab Med 39: 1259-1262.
  • Kallinen J, Heinonen S, Mannermaa A, Ryynanen M (2000) Prenatal diagnosis of fragile X syndrome and the risk of expansion of a premutation. Clin Genet 58: 111-115.
  • Mandel JL, Biancalana V (2004) Fragile X mental retardation syndrome: from pathogenesis to diagnostic issues. Growth Horm IGF Res 14: S158-S165.
  • Meguid NA, Abdel-Raouf ER, Dardir AA, El-Awady MK (2007) Prevalence of fragile X syndrome among school-age Egyptian males. World J Pediatr 3: 271-275.
  • Morrow EM, Yoo SY, Flavell SW, Kim TK, Lin Y, Hill RS, Mukaddes NM, Balkhy S, Gascon G, Hashmi A, Al-Saad S, Ware J, Joseph RM, Greenblatt R, Gleason D, Ertelt JA, Apse KA, Bodell A, Partlow JN, Barry B, Yao H, Markianos K, Ferland RJ, Greenberg ME, Walsh CA (2008) Identifying autism loci and genes by tracing recent shared ancestry. Science 321: 218-223.
  • Murray A, Ennis S, Morton N (2000) No evidence for parent of origin influencing premature ovarian failure in fragile X premutation carriers. Am J Hum Genet 67: 253-254.
  • Nolin SL, Brown WT, Glicksman A, Houck GE Jr, Gargano AD, Sullivan A, Biancalana V, Bröndum-Nielsen K, Hjalgrim H, Holinski-Feder E, Kooy F, Longshore J, Macpherson J, Mandel JL, Matthijs G, Rousseau F, Steinbach P, Väisänen ML, von Koskull H, Sherman SL (2003) Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles. Am J Hum Genet 72: 454-464.
  • Nolin SL, Lewis FA 3rd, Ye LL, Houck GE Jr, Glicksman AE, Limprasert P, Li SY, Zhong N, Ashley AE, Feingold E, Sherman SL, Brown WT (1996) Familial transmission of the FMR1 CGG repeat. Am J Hum Genet 59: 1252-1261.
  • O'Connell CD, Atha DH, Jakupciak JP, Amos JA, Richie K (2002) Standardization of PCR amplification for fragile X trinucleotide repeat measurements. Clin Genet 61: 13-20.
  • Pesso R, Berkenstadt M, Cuckle H, Gak E, Peleg L, Frydman M, Barkai G (2000) Screening for fragile X syndrome in women of reproductive age. Prenat Diagn 20: 611-614.
  • Roberts JE, Bailey DB Jr, Mankowski J, Ford A, Sideris J, Weisenfeld LA, Heath TM, Golden RN (2009) Mood and anxiety disorders in females with the FMR1 premutation. Am J Med Genet B Neuropsychiatr Genet 150B: 130-139.
  • Ryynänen M, Heinonen S, Makkonen M, Kajanoja E, Mannermaa A, Pertti K (1999) Feasibility and acceptance of screening for fragile X mutations in low-risk pregnancies. Eur J Hum Genet 7: 212-216.
  • Saluto A, Brussino A, Tassone F, Arduino C, Cagnoli C, Pappi P, Hagerman P, Migone N, Brusco A (2005) An enhanced polymerase chain reaction assay to detect pre- and full mutation alleles of the fragile X mental retardation 1 gene. J Mol Diagn 7: 605-612.
  • Sherman SL (2000) Premature ovarian failure in the fragile X syndrome. Am J Med Genet 97: 189-194.
  • Tassone F, Hagerman RJ, Taylor AK, Gane LW, Godfrey TE, Hagerman PJ (2000) Elevated levels of FMR1 mRNA in carrier males: a new mechanism of involvement in the fragile-X syndrome. Am J Hum Genet 66: 6-15.
  • Tassone F, Pan R, Amiri K, Taylor AK, Hagerman PJ (2008) A rapid polymerase chain reaction-based screening method for identification of all expanded alleles of the fragile X (FMR 1) gene in newborn and high-risk populations. J Mol Diagn 10: 43-49.
  • Todorov T, Todorova A, Georgieva B, Mitev B (2010) A unified rapid PCR method for detection of normal and expanded trinucleotide alleles of CAG repeats in Huntigon chorea and CGG repeats in Fragile X syndrome. Mol Biotechnol 45: 150-154.
  • Toledano-Alhadef H, Basel-Vanagaite L, Magal N, Davidov B, Ehrlich S, Drasinover V, Taub E, Halpern GJ, Ginott N, Shohat M (2001) Fragile-X carrier screening and the prevalence of premutation and full-mutation carriers in Israel. Am J Hum Genet 69: 351-360.
  • Willemsen R, Oostra BA (2000) FMRP detection assay for the diagnosis of the fragile X syndrome. Am J Med Genet 97: 183-188.
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