Please wait a minute...

Frontiers in Biology

Front. Biol.    2018, Vol. 13 Issue (6) : 464-468     https://doi.org/10.1007/s11515-018-1508-0
RESEARCH ARTICLE
Prevalence of fragile X syndrome among patients with mental retardation in the west of Iran
Peyman Hadi1, Karimeh Haghani2, Ali Noori-Zadeh3, Salar Bakhtiyari2()
1. Department of biology, Sanandaj Branch, Islamic Azad University, Kurdistan, Iran
2. Department of Clinical Biochemistry, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
3. Department of Clinical Biochemistry, Faculty of Paramedicine, Ilam University of Medical Sciences, Ilam, Iran
Download: PDF(98 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

BACKGROUND: Fragile X syndrome (FXS), an X-linked disorder, is the most common cause of inherited mental retardation. This is caused by a trinucleotide CGG repeat expansion (>200) on the fragile X mental retardation 1 gene (FMR1) becoming methylated leading to a deficiency or absence of the FMR1 protein. Determining FXS prevalence in the mentally retarded individuals in the west of Iran was the aim of this study.

METHODS: 200 patients with moderate mental retardation who were clinically suspicious to FXS were screened using cytogenetic and molecular methods. Blood samples were collected and cultured in the specific culture media. The G-Banding method was used for karyotyping and DNA sequencing performed for verifying the results of the cytogenetic tests.

RESULTS: 16 patients (8%) were found to have fragile X syndrome. The results showed that there is no significant association between the fragile X syndrome and economic status and place of residence, however, the relationship between fragile X syndrome and mental retardation in the family history is significant.

CONCLUSION: The frequency of FXS was similar to other reports in the preselected patients. For diagnosis of FXS, chromosome analysis must be accompanied by molecular studies.

Keywords genetic diseases      inborn      FMR1      karyotype      diagnosis      mental retardation     
Corresponding Author(s): Salar Bakhtiyari   
Online First Date: 30 July 2018    Issue Date: 30 November 2018
 Cite this article:   
Peyman Hadi,Karimeh Haghani,Ali Noori-Zadeh, et al. Prevalence of fragile X syndrome among patients with mental retardation in the west of Iran[J]. Front. Biol., 2018, 13(6): 464-468.
 URL:  
http://journal.hep.com.cn/fib/EN/10.1007/s11515-018-1508-0
http://journal.hep.com.cn/fib/EN/Y2018/V13/I6/464
Service
E-mail this article
E-mail Alert
RSS
Articles by authors
Peyman Hadi
Karimeh Haghani
Ali Noori-Zadeh
Salar Bakhtiyari
Age No. of patients %
≤5 y 7 3.5
>5-10 y 52 26
>10-15 y 78 39
>15-20 y 63 31.5
Total 200 100
Tab.1  Distribution of the mental retardation males according to the age of diagnosis
Fragile X-related features Not seen Minor Medium Severe
Long face 80 31 34 55
Large prominent ears 113 25 18 44
Hypre-extensible joints 75 50 26 63
Macro-orchidism 166 0 0 34
Hyperactivity 21 34 50 95
Autistic features 72 30 37 61
Biting the hand 131 14 15 40
Unusual speech pattern 33 70 31 66
Tab.2  Frequency of fragile X features in the mental retardation males
1 Arvio M(2016). Fragile-X syndrome–a 20-year follow-up study of male patients. Clinical genetics, 89 (1399–0004 (Electronic)): 55–9.
2 Ashley C T, Sutcliffe J S- Kunst C B, Kunst C B- Leiner H A, Leiner HA- Eichler E E, Eichler E E- Nelson D L, Nelson D l- Warren S T, Warren S T (1993) . Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG-repeat. Nature genetics, 4 (1061–4036 (Print)): 244–251
3 Berry-Kravis E, Des Portes V, Hagerman R, Jacquemont S, Charles P, Visootsak J, Brinkman M, Rerat K, Koumaras B, Zhu L, Barth G M, Jaecklin T, Apostol G, von Raison F (2016) . Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials. Sci Trans Med, 8 (1946–6242 (Electronic)): 321ra5
4 Bilgen T, Keser I, Mihci E, Mihci E, Haspolat S, Haspolat S, Tacoy S, Tacoy S, Luleci G, Luleci G (2005). Molecular analysis of fragile X syndrome in Antalya Province. Ind J Med Sci, 59 (0019–5359 (Print)): 150–155
5 Brown W T, Houck Ge Jr- Jeziorowska A, Jeziorowska A, Levinson F N, Levinson F n, Ding X, Ding X, Dobkin C, Dobkin C, Zhong N, Zhong N, Henderson J, Henderson J, Brooks S S, Brooks S s, Jenkins E C, Jenkins E C (‎1993) . Rapid fragile X carrier screening and prenatal diagnosis using a nonradioactive PCR test. JAMA, 270 (13): 1569–1575
6 Budimirovic D B, Kaufmann W E (2011). What can we learn about autism from studying fragile X syndrome? Dev Neurosci, 33 (5) :379
7 Butler M G, Hamill T (1995). Blood specimens from patients referred for cytogenetic analysis: Vanderbilt University experience from 1985 to 1992. Southern medical journal, 88 (0038–4348 (Print)): 309–314
8 Carpenter N J, Leichtman L G, Leichtman L G, Say B, Say B (1982). Fragile X-linked mental retardation. A survey of 65 patients with mental retardation of unknown origin. Am J Dis Child, 136 (0002–922X (Print)): De Boulle K, Verkerk A J, Reyniers E, Vits L, Hendrickx J, Van Roy B, Van den Bos F, de Graaff E, Oostra B A, Willems P J (1993). A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat Genet, 3(1): 31–35
9 Demirhan O, Taştemir D, Diler R S, Firat S, Avci A (2003). A cytogenetic study in 120 Turkish children with intellectual disability and characteristics of fragile X syndrome. Yonsei Med J, 44(4): 583–592
https://doi.org/10.3349/ymj.2003.44.4.583 pmid: 12950112
10 Dewald G W, Buckley D D, Spurbeck J L, Jalal S M (1992). Cytogenetic guidelines for fragile X studies tested in routine practice. Am J Med Genet, 44(6): 816–821
https://doi.org/10.1002/ajmg.1320440620 pmid: 1481854
11 Dolen G, Osterweil E, Rao B S S, Rao B S, Smith G B, Smith G B, Auerbach B D,Auerbach B D, Chattarji S, Chattarji S, Bear M F, Bear M F (2007). Correction of fragile X syndrome in mice. Neuron, 56 (0896–6273 (Print)): 955–962
12 Dölen G, Carpenter R L, Ocain T D, Bear M F (2010). Mechanism-based approaches to treating fragile X. Pharmacol Ther, 127(1): 78–93
https://doi.org/10.1016/j.pharmthera.2010.02.008 pmid: 20303363
13 Eichler E E, Holden Jj- Popovich B W, Popovich Bw- Reiss A L, Reiss A L, Snow K, Snow K, Thibodeau S N, Thibodeau Sn- Richards C S, Richards C S, Ward P A, Ward P A, Nelson D L, Nelson D L (1994) . Length of uninterrupted CGG repeats determines instability in the FMR1 gene. Nature genetics, 8 (1061–4036 (Print)): 88–94.9
14 Eichler E E, Richards S, Gibbs R A, Gibbs R A, Nelson D L, Nelson D L (1993). Fine structure of the human FMR1 gene. Hum Mol Genet, 2 (8): 684-685
15 Feng Y, Lakkis L, Devys D, Devys D, Warren S T, Warren S T (1995). Quantitative comparison of FMR1 gene expression in normal and premutation alleles. Am J Hum Genet, 56 (0002–9297 (Print)): 106–113
16 Eichler E E, Richards S, Gibbs R A, Gibbs R A, Nelson D L, Nelson D L. Fine structure of the human FMR1 gene 19931105 DCOM- 19931105.
17 Froster-Iskenius U, Felsch G, Schirren C, Schwinger E (1983). Screening for fra(X)(q) in a population of mentally retarded males. Hum Genet, 63(2): 153–157
https://doi.org/10.1007/BF00291535 pmid: 6682403
18 Froster-Iskenius U, Felsch G, Felsch G- Schirren C, Schirren C, Schwinger E, Schwinger E (1983). Screening for fra(X)(q) in a population of mentally retarded males. Hum Genet, 63 (0340–6717 (Print)): 153–7.
19 Fu Y H, Kuhl D P, Pizzuti A, Pizzuti A, Pieretti M, Pieretti M, Sutcliffe J S, Sutcliffe J S, Richards S, Richards S, Verkerk A J, Verkerk A J, Holden J J, Holden J J, Fenwick R G, Jr., Fenwick RG Jr, Warren S T, Warren S T (1991) . Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell, 67 (0092–8674 (Print)): 1047–1058
20 Grigsby J (2016). The fragile X mental retardation 1 gene (FMR1): historical perspective, phenotypes, mechanism, pathology, and epidemiology. The Clinical neuropsychologist, 30 (1744–4144 (Electronic)): 815–33.
21 Gustavson K H, Blomquist H K, Blomquist H K, Holmgren G, Holmgren G (1986) . Prevalence of the fragile-X syndrome in mentally retarded boys in a Swedish county. American journal of medical genetics, 23 (0148–7299 (Print)): 581–7
22 Hagerman R J, Berry-Kravis E, Kaufmann W E, Kaufmann W E, Ono M Y, Ono M Y, Tartaglia N, Tartaglia N- Lachiewicz A, Lachiewicz A, Kronk R, Kronk R, Delahunty C, Delahunty C, Hessl D, Hessl D, Visootsak J, Visootsak J, Picker J, Picker J, Gane L,Gane L, Tranfaglia M, Tranfaglia M (2009). Advances in the treatment of fragile X syndrome. Pediatrics, 123 (1098–4275 (Electronic)): 378–390
23 Hagerman R J, Berry-Kravis E, Kaufmann W E, Ono M Y, Tartaglia N, Lachiewicz A, Kronk R, Delahunty C, Hessl D, Visootsak J, Picker J, Gane L, Tranfaglia M (2009). Advances in the treatment of fragile X syndrome. Pediatrics, 123(1): 378–390
https://doi.org/10.1542/peds.2008-0317 pmid: 19117905
24 Hinds H L, Ashley Ct- Sutcliffe J S, Sutcliffe J S, Nelson D L, Nelson D L, Warren S T, Warren St- Housman D E, Housman De- Schalling M, Schalling M (1993) . Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome. Nat Genet, 3 (1061–4036 (Print)): 36–43
25 Iqbal M A, Sakati N- Nester M, Nester M- Ozand P, Ozand P (2000). Cytogenetic diagnosis of fragile X syndrome: study of 305 suspected cases in Saudi Arabia. Annals of Saudi medicine, 20 (0256–4947 (Print)): 214–217
26 Jenkins E C, Genovese M, Duncan C J, Gu H, Stark-Houck S, Li S Y, Henderson J, Morys I, Brown W T (1994). Occurrence of aneuploidy for the X chromosome in over 1,300 unrelated specimens screened for the fragile X chromosome. Am J Med Genet, 51(4): 452–453
https://doi.org/10.1002/ajmg.1320510430 pmid: 7943017
27 Jiraanont P A-Ohoo, Kumar M, Tang H T, Espinal G, Hagerman P J, Hagerman R J, Chutabhakdikul N, Tassone F (2017) . Size and methylation mosaicism in males with Fragile X syndrome. Expert review of molecular diagnostics, 17 (1744–8352 (Electronic)): 1023–1032
28 Kunst C B, Warren S T (1994) . Cryptic and polar variation of the fragile X repeat could result in predisposing normal alleles. Cell, 77 (0092–8674 (Print)): 853–861
29 Lozano R, Martinez-Cerdeno V, Hagerman R J (2015) . Advances in the Understanding of the Gabaergic Neurobiology of FMR1 Expanded Alleles Leading to Targeted Treatments for Fragile X Spectrum Disorder. Current pharmaceutical design, 21 (1873–4286 (Electronic)): 4972–9.
30 Motulsky A G (1993). Mendelian inheritance in man: catalogs of autosomal dominant, autosomal recessive, and X–linked phenotypes. JAMA, 269(15): 2003
https://doi.org/10.1001/jama.1993.03500150115041
31 Neri G, Sanfilippo S, Pavone L, Pavone L, Mollica F, Mollica F, Barberi I, Barberi I, Giuffre L, Giuffre L, Romano C, Romano C, Mattina T, Mattina T, Cammarata M, Cammarata M, Ragusa M G, Ragusa M G (1988) . The fragile X in Sicily: an epidemiological survey. American journal of medical genetics, 30 (0148–7299 (Print)): 665–672
32 Pouya A R, Abedini Ss- Mansoorian N, Mansoorian N, Behjati F, Behjati F, Nikzat N, Nikzat N- Mohseni M, Mohseni M, Nieh S E, Nieh S E, Abbasi Moheb L, Abbasi Moheb L, Darvish H, Darvish H, Monajemi G B, Monajemi Gb- Banihashemi S, Banihashemi S, Kahrizi K, Kahrizi K, Ropers H H, Ropers Hh- Najmabadi H, Najmabadi H (2009). Fragile X syndrome screening of families with consanguineous and non-consanguineous parents in the Iranian population. European journal of medical genetics, 52 (1878–0849 (Electronic)): 170–3.
33 Proops R, Webb T (1981). The ‘fragile’ X chromosome in the Martin-Bell-Renpenning syndrome and in males with other forms of familial mental retardation. J Med Genet, 18(5): 366–373
https://doi.org/10.1136/jmg.18.5.366 pmid: 7328617
34 Raspa M, Wheeler A C, Riley C (2017). Public Health Literature Review of Fragile X Syndrome. Pediatrics, 139 (1098–4275 (Electronic)): S153–S71.
35 Rousseau F, Heitz D, Biancalana V, Biancalana V, Blumenfeld S, Blumenfeld S, Kretz C, Kretz C- Boue J, Boue J, Tommerup N, Tommerup N, Van Der Hagen C, Van Der Hagen C, De Lozier-Blanchet C, DeLozier-Blanchet C, Croquette M F, Croquette M F (1991). Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. The New England journal of medicine, 325 (0028–4793 (Print)): 1673–81.
36 Snow K, Doud L K, Hagerman R, Hagerman R, Pergolizzi R G, Pergolizzi R G, Erster S H, Erster S H, Thibodeau S N, Thibodeau S N (1993). Analysis of a CGG sequence at the FMR-1 locus in fragile X families and in the general population. Am J Hum Genet, 53 (0002–9297 (Print)): Snow K, Tester Dj- Kruckeberg K E, Kruckeberg Ke- Schaid D J, Schaid Dj- Thibodeau S N, Thibodeau S N.(1994) Sequence analysis of the fragile X trinucleotide repeat: implications for the origin of the fragile X mutation. Human molecular genetics, 3 (0964–6906 (Print)): 1543–51.
37 Sutherland G R (1977). Fragile sites on human chromosomes: demonstration of their dependence on the type of tissue culture medium. Science, 197 (0036–8075 (Print)): 265–266
38 Wohrle D, Kotzot D, Hirst M C, Hirst M C, Manca A, Manca A, Korn B, Korn B- Schmidt A, Schmidt A, Barbi G, Barbi G- Rott H D, Rott H D, Poustka A, Poustka A, Davies K E, Davies K E (1992) . A microdeletion of less than 250 kb, including the proximal part of the FMR-I gene and the fragile-X site, in a male with the clinical phenotype of fragile-X syndrome. American journal of human genetics, 51 (0002–9297 (Print)): 299–306.
39 Yu S, Pritchard M, Kremer E, Kremer E, Lynch M, Lynch M, Nancarrow J, Nancarrow J- Baker E, Baker E- Holman K, Holman K- Mulley J C, Mulley J C, Warren S T, Warren St- Schlessinger D, Schlessinger D (1991). Fragile X genotype characterized by an unstable region of DNA. Science, 252 (0036–8075 (Print)): 1179–81.
40 Zhang H, Xia J- Li L, Li L- Dai H, Dai H- Lu H, Lu H (1990). The high resolution G band of human chromosomes at 1200 band stage. Acta Genetica Sinica, 17 (0379–4172 (Print)):
Related articles from Frontiers Journals
[1] Tian XIAO, Lei BAO, Hongbin JI. Finding biomarkers for non-small cell lung cancer diagnosis and prognosis[J]. Front Biol, 2012, 7(1): 14-23.
[2] Richard D. Smrt, Xinyu Zhao, . Epigenetic regulation of neuronal dendrite and dendritic spine development[J]. Front. Biol., 2010, 5(4): 304-323.
[3] LIU Bo, CHEN Chengbin, LI Xiulan, QI Liwang, HAN Suying. Karyotype analysis and physical mapping of 45S rDNA in eight species of Sophora, Robinia, and Amorpha[J]. Front. Biol., 2006, 1(3): 290-294.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed