CoChat
Sign Up
Cited by 60Genetics and Neurodevelopmental DisordersDown syndrome and intellectual disability researchGenomics and Rare Diseases

Screening for fragile X syndrome.

Open access
Murray, Cuckle, Taylor, Hewison·1997·Health Technology Assessment
DOI 10.3310/hta1040
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND AND AIM OF REVIEW. In 1991, the gene responsible for fragile X syndrome, a common cause of learning disability, was discovered. As a result, diagnosis of the disorder has improved and its molecular genetics are now understood. This report seems to provide the information needed to decide whether to use DNA testing to screen for the disorder. HOW THE RESEARCH WAS CONDUCTED. A literature search of electronic reference databases of published and 'grey' literature was undertaken together with hand searching of the most recent publications. RESEARCH FINDINGS. NATURAL HISTORY. Physical characteristics of fragile X syndrome include facial atypia, joint laxity and, in boys, macro-orchidism. Most affected males have moderate-to-severe learning disabilities with IQs under 50 whereas most females have borderline IQs of 70-85. Behavioural problems are similar to those seen with autism and attention-deficit disorders. Although fragile X syndrome is not curable there are a number of medical, educational, psychological and social interventions that can improve the symptoms. About 6% of those with learning disabilities tested in institutions have fragile X syndrome. Population prevalence figures are 1 in 4000 in males and 1 in 8000 in females. GENETICS. The disorder is caused by a mutation in a gene on the X chromosome which includes a trinucleotide repeat sequence. The mutation is characterized by hyper-expansion of the repeat sequence leading to down-regulation of the gene. In males an allele with repeat size in excess of 200, termed a full mutation (FM), is always associated with the affected phenotype, whereas in females only half are affected. Individuals with alleles having repeat size in the range 55-199 are unaffected but in females the sequence is heritably unstable so that it is at high risk of expansion to an FM in her offspring. This allele is known as a pre-mutation (PM) to contrast it with the FM found in the affected individual. No spontaneous expansions directly from a normal allele to an FM have been observed. SCREENING STRATEGIES. The principal aims of screenng for fragile X syndrome is to reduce the birth prevalence of the disorder, by prenatal diagnosis and selective termination of pregnancy, or by reducing the number of pregnancies in women who have the FM or PM alleles. Possible screening strategies are: routine antenatal testing of apparently low risk pregnancies, preconceptual testing of young women, and systematic testing in affected families ('cascade' screening). A secondary aim is to bring forward the diagnosis of affected individuals so that they might benefit from early treatment. Active paediatric screening and neonatal screening could achieve this but there is no direct evidence of any great benefit from early diagnosis. SCREENING TESTS. Cytogenetic methods are unsuitable for screening purposes. Southern blotting of genomic DNA can be used but is inaccurate in measuring the size of small PMs, there is a long laboratory turnaround time, and it is relatively expensive. The best protocol is to amplify the DNA using polymerase chain reaction on all samples, and when there is a possible failure to amplify, a Southern blot.(ABSTRACT TRUNCATED)

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3310/hta1040

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 441 · Cited by 60

Research works printed but not linked: 141

  1. Abrams MT, Reiss AL, 1995. Quantitative brain imaging studies of fragile-X syndrome. Dev Brain Dysfunction;8(4-6):187-98.
  2. Ashley CT Jr, Wilkinson KD, Reines D, Warren ST, 1993a. FMR1 protein: conserved RNP family domains and selective binding. Science;262:563-6.
  3. Bakker C, Degraaff E, Zhong N, Willemsen R, Oostra B, 1995. Instability of the CGG repeat and expression of FMR1 protein in a male-patient with a lung-tumor. Am J Human Genetics;57:1359.
  4. Billings P, Hubbard R, 1994. Fragile X testing: who benefits? Genewatch;9:1-3.
  5. Bodurtha J, Tams L, Jackson-Cook C, 1992. Prenatal genetic counseling: what is fragile X [review]? Virginia Med Quart;119(2):97-8.
  6. Brøndum Nielson K, Tommerup N, Dyggve H, Schou C, 1981. Macro-orchidism, mental retardation and the fragile X [letter]. N Engl J Med;305:1348.
  7. Brøndum Nielson K, Tommerup N, Dyggve H, Schou C, 1982. Macro-orchidism and fragile X mentally retarded males. Human Genetics;61:113-17.
  8. Brown CA, Brasington CK, Grass FS, 1995. Paternal transmission of a full mutation in the FMR1 gene - identification of paternal CGG repeat sizes in multiple tissues. Am J Human Genetics;57:A335.
  9. Brown WT, Jenkins EC, Goonewardena P, Miezejeski C, Atkin J, Devys D, 1992. Prenatally detected fragile X females: long-term follow-up studies show high risk of mental retardation. Am J Med Genetics;43:96-102.
  10. Brown WT, Nolin S, Houck G, et al, 1996. Prenatal- diagnosis and carrier screening for fragile X by PCR. Am J Med Genetics;64:191-5.
  11. Bullock S, Felix CA, Butterworth MA, Stevenson K, Williams D, 1995. The use of molecular DNA testing to distinguish between mutations at the fragile X -A and -E sites. J Med Genetics;32:154.
  12. Bundey S, Norman E, 1993. Population screening for fragile-X syndrome [letter]. Lancet;341:770.
  13. Butler MG, Pratesi R, Vnencak-Jones CL, 1994. Molecular genetic screening in cytogenetically normal mentally retarded males with manifestations of fragile X syndrome [letter]. Am J Med Genetics;51:315-6.
  14. Caskey CT, 1994. Fragile X syndrome. improving understanding and diagnosis [editorial; comment]. JAMA;271:552-3.
  15. Castellvi-Bel S, Mila M, Soler A, et al, 1995. Prenatal- diagnosis of fragile-X syndrome-(CGG)n expansion and methylation of chorionic villus samples. Prenatal Diag;9:801-7.
  16. Catalono RA, 1990. Down's syndrome. Surv Opthalmol;34:385.
  17. Chiurazzi P, Kozak L, Neri G, 1994a. Unstable triplets and their mutational mechanism: size reduction of the CGG repeat vs. germline mosaicism in the fragile X syndrome [review]. Am J Med Genetics;51:517-21.
  18. Chiurazzi P, Genuardi M, Kozak L, et al, 1996. Fragile-X founder chromosomes in Italy -a few initial events and possible explanation for their heterogeneity. Am J Med Genetics;64:209-15.
  19. Clayton-Smith J, 1995. Specification of the neuro- behavioural phenotype in males with fragile X syndrome. J Med Genetics;32:853.
  20. Cohen IL, 1995. Behavioral profiles of autistic and nonautistic fragile-x males. Dev Brain Dysfunction;8:252-69.
  21. Craft N, 1995. Study supports screening for the fragile X syndrome [news]. BMJ;310:148.
  22. Cronister A, 1995. Genetic-counseling issues. Dev Brain Dysfunction;8:353-8.
  23. Davies KE, 1992. Human genetics. The costs of instability [news]. Nature;356:15.
  24. de Arce MA, 1984. Verification of Lyon's hypothesis in fragile X carriers [letter]. Human Genetics;68:346-7.
  25. de Vries BBA, Robinson H, Stolte-Dijkstra I, et al, 1995a. General overgrowth in the fragile X syndrome: variability in the phenotypic expression of the FMR1 mutation. J Med Genetics;32:764-9.
  26. de Vries BBA, van den Ouweland AMV, Mohkamsing S, et al, 1995b. Acceptance of screening for the fragile-X syndrome among 1878 mentally-retarded individuals in institutes and special schools in the Netherlands. Am J Human Genetics;57:1705.
  27. Eichler EE, Nelson DL, 1996. Genetic-variation and evolutionary stability of the FMR1-cgg repeat in six closed human-populations. Am J Med Genetics;64:220-5.
  28. Feng Y, Zhang F, Lokey LK, et al, 1995b. Translational suppression by trinucleotide repeat expansion at FMR1. Science;268:731-4.
  29. Fisch GS, 1993. What is associated with the fragile X syndrome [review]? Am J Med Genetics;48:112-21.
  30. Fryns JP, Curfs LM, Cassiman JJ, van den Berghe H, 1992. The fragile-X syndrome after the discovery of the FMR-1 gene. The clinical geneticist faced with the unravelled enigmas and persisting difficulties in genetic counseling [editorial]. Genetic Counselling;3:175-7.
  31. Fu YH, Kuhl DP, Pizzuti A, et al, 1991. Variation of the CGG repeat at the fragile X site results in genetic nstability: resolution of the Sherman paradox. Cell;67:1047-58.
  32. Fu YH, Pizzuti A, Fenwick RG, et al, 1992. An unstable triplet repeat in a gene related to myotonic dystrophy. Science;255:1256-8.
  33. Glass L, 1995. Females with fragile-X -a parent's perspective. Dev Brain Dysfunction;8:363-6.
  34. Goonewardena P, Zhang J, 1995. A single tube nonradioactive PCR assay for the detection of the full spectrum of FMR1 CGG repeats seen in the normal carrier and fragile-X syndrome individuals. Am J Human Genetics;57:1914.
  35. Grasso M, Perroni L, Colella S, et al, 1996. Prenatal- diagnosis of 30 fetuses at risk for fragile-X-syndrome. Am J Med Genetics;64:187-90.
  36. Gu Y, Shen Y, Gibbs RA, Nelson DL, 1996. Identification of FMR2, a novel gene associated with the FRAXE CGG repeat and CpG island. Nature Genetics;13:109-13.
  37. Hagerman RJ, 1987. Fragile X syndrome. Curr Problems Ped;17:621-74.
  38. Hagerman RJ, Amiri K, Cronister A, 1991. Fragile X checklist. Am J Med Genetics;38:283-7.
  39. Hagerman RJ, Riddle JE, Roberts LS, Breese K, Fulton M, 1995. Survey of the efficacy of clonidine in fragile-X syndrome. Dev Brain Dysfunction;8:336-44.
  40. Hansen RS, Gartler SM, Scott CR,Chen SH, Laird CD, 1992. Methylation analysis of CGG sites in the CpG island of the human FMR1 gene. Human Molec Genetics;1:571-8.
  41. Hirst MC, Knight S, Cavies K, et al, 1991b. Prenatal diagnosis of fragile X syndrome. Lancet;338:956-7.
  42. Hirst MC, Barnicoat A, Flynn G, et al, 1993b. The identification of a third fragile site, FRAXF in Xq27-28 distal to both FRAXA and FRAXE. Human Molec Genetics;2:197-200.
  43. Hirst MC, Grewal P, Flannery A, et al, 1995. Two new cases of FMR1 deletion associated with mental impairment. Am J Human Genetics;56:67-74.
  44. Holden JJA, Chalifoux M, Wing M, et al, 1995a. Distribution and frequency of FMR1 CGG repeat number in institutionalised developmentally disabled individuals. Dev Brain Dysfunction;8:302-9.
  45. Holden JJA, Chalifoux M, Julieninalsingh C, et al, 1995b. Lack of expansion of triplet repeats in the FMR1, FRAXE and FRAXF genes in multiplex male families with autism and pervasive developmental disorders. Am J Human Genetics;57:1920.
  46. Holden JJA, Chalifoux M, Wing M, et al, 1995c. Distribution and frequency of FMR1 CGG repeat numbers in the general-population. Dev Brain Dysfunction;8:405-7.
  47. Howard-Peebles PN, Maddalena A, Black SH, Schulman JD, 1993. Population screening for fragile-X syndrome [letter]. Lancet;341:770.
  48. Howard-Peebles PN, Maddalena A, Spence WC, et al, 1994. Fragile X screening: what is the real issue [letter]? Am J Med Genetics;53:382.
  49. Howard-Peebles PN, Maddalena A, Black SH, Levinson G, Bick DD, Schulman JD, 1995. Fragile X screening in pediatric and obstetrical patients. Dev Brain Dysfunction;8:408-10.
  50. Hulten M, Armstrong S, Barlow A, et al, 1995. Germ-line mosaicism investigations in the fragile X syndrome. British Medical Genetics Conference 1995; Abstract 123.
  51. Jenkins EC, Genovese M, Duncan CJ, et al, 1994a. Occurrence of aneuploidy for the X chromosome in over 1300 unrelated specimens screened for the fragile X chromosome [letter]. Am J Med Genetics;51:452-3.
  52. Jenkins EC, Houck GE, Ding XH, et al, 1995b. An update on fragile-X prenatal-diagnosis -end of the cytogenetic testing era. Dev Brain Dysfunction;8:293-301.
  53. Jennings M, Hall JG, Hoehn H, 1980. Significance of phenotypic and chromosomal abnormalities in X-linked mental retardation. Am J Med Genetics;7:417-32.
  54. Johnson JP, Curry C, Micek M, Louie E, Abrams L, Dietz L, 1995. Transmission of stable and unstable premutations from great-grandmother and great- grandfather respectively -lessons for genetic- counseling in fragile-X syndrome families. Am J Human Genetics;57:1407.
  55. Koide R, Ikeuchi T, Onodera O, et al, 1994. Unstable expansion of CAG repeat in hereditary dentatorubral- pallidolusian atrophy (DRPLA). Nature Genetics;6:9-13.
  56. Kolehmainen K, Karant Y, 1994. Modelling methylation and IQ scores in fragile X females and mosaic males. Am J Med Genetics;51:328-38.
  57. Kremer EJ, Pritchard M, Lynch M, et al, 1991. Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science;252:1711-4.
  58. Laing S, Partington M, Robinson H, Turner G, 1991. Chemical screening score for the fragile X (Martin-Bell) syndrome. Am J Med Genetics;38:256-9.
  59. Lauria DP, Webb MJ, McKenzie P, Hagerman R, 1992. The economic impact of the fragile X syndrome on the state of Colorado. In: Hagerman RJ, McKenzie P, editors. Proceedings of International Fragile X Conference; chap 52:393-405.
  60. Lubs HA, 1969. A marker X-chromosome. Am J Human Genetics;21:231-44.
  61. Lubs HA, Chiurazzi P, Arena JF, Schwartz C, Tranebjaerg L, Neri G, 1996. XLMR genes -update 1996. Am J Med Genetics;64:147-57.
  62. Mandel JL, 1993. Questions of expansion [news]. Nature Genetics;4:8-9.
  63. Mandel JL, Biancalana V, Boiux JC, Cossee M, 1994. Screening for the fragile X syndrome mental retardation syndrome. New Horizons Neonat Screen;1041(71):261-72.
  64. Mazurczak T, Bocian E, Milewski M, et al, 1996. Frequency of fra-x-syndrome among institutionalized mentally-retarded males in Poland. Am J Med Genetics;64:184-6.
  65. Mazzocco MM, Pennington BF, Hagerman RJ, 1993. The neurocognitive phenotype of female carriers of fragile X: additional evidence for specificity. J Dev Behav Ped;14:328-35.
  66. McConkie-Rosell A, Lachiewicz AM, Spiridigliozzi GA, et al, 1993. Evidence that methylation of the FMR-1 locus is responsible for variable phenotypic expression of the fragile X syndrome. Am J Human Genetics;53:800-9.
  67. McConkie-Rosell A, Robinson H, Wake S, Staley L, Heller K, Cronister A, 1995a. Educating extended family members about the inheritance of the fragile-X syndrome. Dev Brain Dysfunction;8:390-5.
  68. McConkie-Rosell A, Robinson H, Wake S, Staley LW, Heller K, Cronister A, 1995b. Dissemination of genetic risk information to relatives in the fragile X syndrome: guidelines for genetic counsellors. Am J Med Genetics;59:426-30.
  69. Migeon BR, 1993. NICHD conference. Role of DNA methylation in X inactivation and the fragile X syndrome. Am J Med Genetics;46:685-6.
  70. Monckton DG, Caskey CT, 1995. Unstable triplet repeat diseases [review]. Circulation;91:513-20.
  71. Mornet E, Chateau C, Taillandier A, et al, 1994. FRAXAC2 instability [letter]. Nature Genetics;7:122-3.
  72. Morton JE, Rindl PM, Bullock S, Bundey S, Webb T, 1995. Fragile-X syndrome is less common than previously estimated. J Med Genetics;32:144-5.
  73. Musumeci SA, Ferri R, Colognola M, Neir G, Sanfilippo S, Bergonzi P, 1988. Prevalence of a novel epileptogenic EGG pattern in the Martin-Bell syndrome. Am J Med Genetics;30:207-12.
  74. Nagafuchi S, Yanagisawa H, Sato K, et al, 1994. Dentatorubral and pallidolusian atrophy expansion of an unstable CAG trinucleotide on chromosome 12. Nature Genetics;6:14-18.
  75. Nakahori Y, 1995. The incidence of the fragile X syndrome [in Japanese -commentary on Nanba et al, 1995]. Brain Dev;17:322.
  76. Nanba E, Kohno Y, Matsuda A, et al, 1995. Nonradio- active DNA diagnosis for the fragile X syndrome in mentally-retarded Japanese males. Brain Dev;7:317-21.
  77. Nelson DL, 1995. The fragile X syndrome. Sem Cell Biol;6(1):5-11.
  78. Nelson DL, Warren ST, 1993. Trinucleotide repeat instability: when and where [news -comment]? Nature Genetics;4:107-8.
  79. Nelson DL, Kunst CB, Lugenbeel KA, Ryder OA, Warren ST, Eichler EE, 1995. Evolution of the cryptic FMR1 CGG repeat. Am J Human Genetics;57:211.
  80. Nolin SL, Glicksman A, Lewis FA, et al, 1995. Evidence for a familial factor involved in CGG repeat expansion in fragile-X syndrome. Am J Human Genetics;57:965.
  81. Orr HT, Chung M-Y, Banfi S, et al, 1993. Expansion of an unstable CAG repeat in spinocerebellar ataxia type 1. Nature Genetics;4:221-6.
  82. Paika IJ, Lai F, McAllister NM, Miller WA, 1984. The fragile-X marker survey: preliminary report on the screening of suspected fragile X syndrome patients at the Fernald State School. Am J Human Genetics;36:108S.
  83. Pennington BF, O'Connor RA, Sudhalter V, 1991. Towards a neuropsychology of fragile X syndrome. In: Hagerman RJ, Silverman AC. Fragile X syndrome: diagnosis, treatment and research. Baltimore: Johns Hopkins University Press.
  84. Richards RI, Sutherland GR, 1992. Heritable unstable DNA sequences [news]. Nature Genetics;1:7-9.
  85. Richards RI, Holman K, Friend K, et al, 1994a. FRAXAC2 instability [letter; comment]. Nature Genetics;7:122-3.
  86. Robinson H, Wake S, Wright F, Laing S, Turner G, 1996. Informed choice in fragile-X syndrome and its effects on prevalence. Am J Med Genetics;64:198-202.
  87. Rossiter BJ, Caskey CT, 1992. The human genome project and clinical medicine [review]. Oncology;6(11):61-8, 71, 75-6.
  88. Rousseau F, Rouillard P, Morel ML, Khandjian EW, Morgan N, 1995. Prevalence of carriers of premutation- size alleles of the FMR1 gene and implications for the population-genetics of the fragile-X syndrome. Am J Human Genetics;57:1006-18.
  89. Roy JC, Johnsen J, Breese K, Hagerman R, 1995. Fragile-x syndrome -what is the impact of diagnosis on families? Dev Brain Dysfunction;8:327-35.
  90. Ryynänen M, Kirkinen P, Mannermaa A, Saarikoski S, 1995. Carrier diagnosis of the fragile X syndrome - a challenge in antenatal clinics. Am J Obstet Gynecol;172:1236-9.
  91. Schinzel A, Largo RH, 1985. The fragile X syndrome (Martin-Bell syndrome): clinical and cytogenetic findings in 16 prepubertal boys and in four of their families. Helv Pediatr Acta;40:133-52.
  92. Shapiro LR, 1991b. The fragile X syndrome -clinical overview [review]. Prog Clin Biol Res;368:3-14.
  93. Shastry BS, 1994. Heritable trinucleotide repeats and neurological disorders [review]. Experientia;50:1099-105.
  94. Sherman SL, 1991. Genetic epidemiology of the fragile X syndrome with special reference to genetic counseling [review]. Prog Clin Biol Res;368:79-99.
  95. Smith SE, 1993. Cognitive deficits associated with fragile X syndrome [review]. Mental Retard;31:279-83.
  96. Sobesky WE, Porter D, Pennington BF, Hagerman RJ, 1995. Dimensions of shyness in fragile-X females. Dev Brain Dysfunction;8:280-92.
  97. Spence WC, Black SH, Fallon L, et al, 1996. Molecular fragile-x screening in normal populations. Am J Med Genetics;64:181-3.
  98. Staley LW, Tylor AK, Mcgavran L, et al, 1995. Identification of cytogenetic abnormalities as a consequence of FMR-1 testing in schools. Dev Brain Dysfunction;8:310-18.
  99. Steyaert J, Borghgraef M, Gulthier C, Fryns JP, van den Berghe H, 1992. Cognitive profiles in adult, normal intelligent female fragile X carriers. Am J Med Genetics;43:116-19.
  100. Storm RL, Pebenito R, Ferretti C, 1987. Opthalmologic findings in the fragile X syndrome. Arch Opthalm;105:1099-1102.
  101. Sudhalter V, Cohen IL, Silverman W, Wolf-Schein EG, 1990. Conversational analyses of males with fragile X, Down's syndrome and autism: comparison of the emergence of deviant language. Am J Mental Retard;94:431-41.
  102. Sutcliffe JS, Nelson DL, Zhang F, et al, 1992. DNA methylation represses FMR-1 transcription in fragile X syndrome. Human Molec Genetics;1:397-400.
  103. Sutherland GR, 1984. Routine diagnostic detection of the fragile X [letter]. J Med Genetics;21:74-5.
  104. Sutherland GR, Baker E, 1990. The common fragile site in band Xq27 of the human X chromosome is not coincident with the fragile X. Clin Genetics;37:167-72.
  105. Sutherland GR, Ledbetter DH, 1989. Report of the Committe on Cytogenetic Markers. Cytogen Cell Genetics;15:452.
  106. Sutherland GR, Richards RI, 1992. Anticipation legitimized: unstable DNA to the rescue [editorial]. Am J Human Genetics;51:7-9.
  107. Sutherland GR, Richards RI, 1995. Simple tandem DNA repeats and human genetic disease [review]. Proc Natl Acad Sci USA;92:3636-41.
  108. Sutherland GR, Baker E, Fratini A, 1985. Excess thymidine induces folate sensitive fragile sites. Am J Med Genetics;22:433-43.
  109. Sutherland GR, Mulley JC, Richards RI, 1993. Fragile X syndrome. The most common cause of familial intellectual handicap [review]. Med J Aust;158:482-5.
  110. Syrrou M, Patsalis PC, Georgiou I, Hadjimarcou MI, Constantinoudeltas CD, Pagoulatos G, 1996. Evidence for high-risk haplotypes and (CGG)n expansion in fragile-X syndrome in the Hellenic population of Greece and Cyprus. Am J Med Genetics;64:234-8.
  111. Tommerup N, 1989. Cytogenetics of the fragile site at Xq27. In: Davies KE, editor. The fragile X syndrome. Oxford: Oxford University Press:103-35.
  112. Tsai MS, Chien TY, Yang YL, Chen HR, Hwang SM, 1995. Identification of the number of the fragile-X syndrome CGG repeat using silver stain. Am J Human Genetics;57:1941.
  113. Tsongalis GJ, Silverman LM, 1993. Molecular pathology of the fragile X syndrome [review]. Arch Path Lab Med;117:1121-5.
  114. Turk J, 1992b. The fragile-X syndrome. On the way to a behavioural phenotype [review]. Br J Psych;160:24-35.
  115. Turk J, 1995a. Fragile X syndrome. Arch Dis Child;72:3-5.
  116. Turner G, Robinson H, Laing S, Purvis-Smith S, 1986. Preventative screening for the fragile X syndrome. N Engl J Med;315:607-9.
  117. Verheij C, de Graaff E, Bakker CE, et al, 1995. Character- isation of FMR1 proteins isolated from different tissues. Human Molec Genetics;4:895-901.
  118. Wake SA, Robinson H, 1995. Assessment of counseling of normal males and normal transmitting male carriers identified in fragile-X families. Dev Brain Dysfunction;8:319-26.
  119. Wang Q, Green E, Barnicoat A, et al, 1993. Cytogenetic versus DNA diagnosis in routine referrals for fragile X syndrome. Lancet;342:1025-6.
  120. Wang Q, Green E, Bobrow M, Mathew CG, 1995b. Screening for the fragile X A and E mutations by automated fluorescent analysis. J Med Genetics;32:153.
  121. Watkiss E, Webb T, 1995. Comparison of methods for studying X inactivation status in females. J Med Genetics;32:151.
  122. Watson MS, Leckman JF, Annex B, et al, 1984. Fragile X in a survey of 75 autistic males [letter]. N Engl J Med;310:1462.
  123. Willard HF, 1996. X-chromosome inactivation and X-linked mental-retardation. Am J Med Genetics;64:21-6.
  124. Willems PJ, 1994. Dynamic mutations hit double figures [news; comment]. Nature Genetics;8:213-5.
  125. Wilmot PL, 1991. Review of cytogenetic data for fragile X detection: lymphocytes and other tissues [review]. Prog Clin Biol Res;368:15-25.
  126. Winter RM, 1987. Population genetics implications of the premutation hypothesis for the generation of the fragile X mentality. Human Genetics;75:269-71.
  127. Winkeler KA, Warren ST, 1995. Variations in the length of the CGG-repeat of FMR-1 affect gene-expression. Am J Human Genetics;57:869.
  128. Wöhrle D, Kotzot D, Hirst MC, et al, 1992a. A micro- deletion of less than 250 kb, including the proximal part of the FMR-1 gene and the fragile-X site, in a male with the clinical phenotype of fragile-X syndrome. Am J Human Genetics;51:299-306.
  129. Wolff PH, Gardner J, Paccia J, Lappen J, 1989. The greeting behaviour of fragile X males. Am J Ment Retard;93:406-11.
  130. Wrighttalamante C, Cheema A, Riddle JE, Luckey D, Taylor A, Hagerman RJ, 1995. A controlled-study of longitudinal IQ changes in females and males with fragile-X syndrome. Am J Human Genetics;57:585.
  131. Young ID, 1993. Diagnosing fragile X syndrome [comment]. Lancet;342:1004-5.
  132. Zhong N, Dobkin C, Brown WT, 1993. A complex mutable polymorphism located within the fragile X gene [see comments]. Nature Genetics;5:248-53.
  133. Zhong N, Liu X, Gou S, et al, 1994. Distribution of FMR-1 and associated microsatellite alleles in a normal Chinese population. Am J Med Genetics;51:417-22.
  134. Zhong N, Curley D, Dobkin C, Brown WT, 1995a. Determination of transcription factors binding to the FMR1 promoter region. Am J Human Genetics;57:880.
  135. Zhong N, Kajanoja E, Smits B, et al, 1996. Fragile-X founder effects and new mutations in Finland. Am J Med Genetics;64:226-33.
  136. Ammala P, Hilesmaa VK, Liukkonben S, Saisto T, Teramo K, von Koskull H, 1993. Randomised trial comparing first-trimester transcervical chorionic villus sampling and second-trimester amniocentesis. Prenatal Diagnos;13:919-27.
  137. Brock DJ, 1994. Carrier screening for cystic fibrosis (review). Prenatal Diagnos;13:1243-52.
  138. Cuckle HS, Wald NJ, 1984. Principles of screening. In: Wald N, editor. Antenatal and neonatal screening for disease. Oxford University Press:1-22.
  139. Mooney G, Lange M, 1993. Antenatal screening: what constitutes benefit? Soc Sci Med;37:873-8.
  140. MRC Working Party on the Evaluation of Chorionic Villus Sampling, 1991. Medical Research Council European trial of chorionic villus sampling. Lancet;337:1491-9.
  141. Thornton J, Lilford RJ, 1995. Decision analysis for medical managers -assessment of screening tests. BMJ;310:791-4.

Authors
Murray, Cuckle, Taylor, & Hewison
Affiliations
University of Leeds (GB)
Venue
Health Technology Assessment
Publisher
National Institute for Health and Care Research
Published
1997
Volume
1
Issue
4
Pages
i-iv, 1
ISSN
  • 1366-5278 (ISSN-L)
  • 2046-4924
DOI
10.3310/hta1040
OpenAlex
W191471975
Cited by
60
References
441
Citations by year
2020: 1 · 2019: 1 · 2018: 2 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 3
FWCI
1.49
Type
journal article
Language
en
Open access
Licence
www.nationalarchives.gov.uk/doc/non-commercial-government-licence/non-commercial-government-licence.htm (unspecified)
Locations
  • Health Technology Assessment (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Health Technology Assessment Programme (93/34/03)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords
fragile X syndrome, genetic screening, trinucleotide repeat expansion, FMR1 gene, full mutation, X-linked inheritance, prenatal diagnosis, family screening, newborn screening, learning disabilities, natural history (disease), prevalence, behavioral problems, prenatal termination, carrier screening, FMR1 repeat expansion
MeSH terms
Costs and Cost Analysis, Fragile X Syndrome, Genetics, Population, Humans, Mass Screening, Prenatal Diagnosis, Prevalence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review