Screening for Expanded Alleles of the FMR1 Gene in Blood Spots from Newborn Males in a Spanish Population
Open accessAbstract
Fragile X syndrome, which is caused by expanded CGG repeats of the FMR1 gene, is associated with a broad spectrum of clinical involvement and is the most common inherited form of intellectual disability. Early diagnosis and intervention are likely to lead to improved outcome for children with fragile X syndrome, but such strategies require better estimates of the frequencies of expanded alleles of the FMR1 gene. In this study, we report the results of a newborn screening study of 5267 male blood spots collected from the Northwest region of Spain as part of the national newborn screening program. The blood spots were screened using a rapid polymerase chain reaction-based method that is capable of identifying the presence of all expanded alleles for both males and females. The screened samples included 199 gray zone alleles, 21 premutation alleles, and two full mutation alleles (1 in 2633). The frequency of premutation alleles was three times higher (1 in 251) than the quoted value of 1 in 813 from a Canadian population and is fully consistent with the results of large-scale Israeli screening studies. Our results demonstrate that newborn screening for the presence of expanded FMR1 alleles is an effective means for defining the distribution of expanded FMR1 alleles in newborn populations; as such, this method is suitable for large-scale newborn screening.
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.
Integrity signals
Registry
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.
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?
Premutation prevalence differs across ethnic groups, being higher in people of mixed European descent than in African American and Hispanic people, and is higher than in previous studies.
“PM prevalence was found to be different in various ethnic groups; it was higher in people of mixed European descent compared with that in African American and Hispanic people (for both males and females) and shows a higher incidence for PM compared with that in previous studies (34,35).”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [34]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Evaluating non-randomised intervention studies
Deeks, J., Dinnes, J., D'Amico, R., Sowden, A., Sakarovitch, C., Song, F., Petticrew, M., & Altman, D. (2003) · Health Technology Assessment · doi:10.3310/hta7270 · Cited by 2,907 · see citing works
Fu, Y.-H., Kuhl, D. P. A., Pizzuti, A., Pieretti, M., Sutcliffe, J. S., Richards, S., Verkert, A. J. M. H., Holden, J. J. A., Fenwick, R. G., Warren, S. T., et al. (1991) · Cell · doi:10.1016/0092-8674(91)90283-5 · Cited by 2,080 · see citing works
Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X
Hagerman, R. J., Leehey, M. A., Heinrichs, W. L., Tassone, F., Wilson, R., Hills, J. D., Grigsby, J., Gage, B. F., & Hagerman, P. J. (2001) · Neurology · doi:10.1212/wnl.57.1.127 · Cited by 966 · see citing works
Self-citationFMR1 and the fragile X syndrome: Human genome epidemiology review
Crawford, D. C., Acuña, J. M., & Sherman, S. L. (2001) · Genetics in Medicine · doi:10.1097/00125817-200109000-00006 · Cited by 711 · see citing works
The Fragile-X Premutation: A Maturing Perspective
Hagerman, P. J., & Hagerman, R. J. (2004) · The American Journal of Human Genetics · doi:10.1086/386296 · Cited by 520 · see citing works
Self-citationFragile X Syndrome: Diagnosis, Treatment, And Research
Silverman, & Cronister, A. (1991) · Johns Hopkins University Press eBooks · Cited by 481 · see citing works
Rousseau, F., Rouillard, P., Morel, M. L., Khandjian, E. W., & Morgan, K. (1995) · Europe PMC (PubMed Central) · Cited by 361 · see citing works
Tassone, F., Pan, R., Amiri, K. M. A., Taylor, A. K., & Hagerman, P. J. (2007) · Journal of Molecular Diagnostics · doi:10.2353/jmoldx.2008.070073 · Cited by 350 · see citing works
Self-citationThe fragile X prevalence paradox
Hagerman, P. J. (2008) · Journal of Medical Genetics · doi:10.1136/jmg.2008.059055 · Cited by 343 · see citing works
Self-citationFragile X‐associated tremor/ataxia syndrome: Clinical features, genetics, and testing guidelines
Berry‐Kravis, E., Abrams, L. J., Coffey, S. M., Hall, D. A., Greco, C., Gane, L. W., Grigsby, J., Bourgeois, J. A., Finucane, B. M., Jacquemont, S., et al. (2007) · Movement Disorders · doi:10.1002/mds.21493 · Cited by 331 · see citing works
Self-citationFARZIN, F., PERRY, H., HESSL, D., LOESCH, D., COHEN, J., BACALMAN, S., GANE, L., TASSONE, F., HAGERMAN, P., & HAGERMAN, R. (2006) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/00004703-200604002-00012 · Cited by 325 · see citing works
Self-citationDombrowski, C. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.4.371 · Cited by 289 · see citing works
The fragile X premutation: into the phenotypic fold
Hagerman, R. J., & Hagerman, P. J. (2002) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00299-x · Cited by 259 · see citing works
Self-citationFragile-X Carrier Screening and the Prevalence of Premutation and Full-Mutation Carriers in Israel
Toledano‐Alhadef, H., Basel‐Vanagaite, L., Magal, N., Davidov, B., Ehrlich, S., Drasinover, V., Taub, E., Halpern, G. J., Ginott, N., & Shohat, M. (2001) · The American Journal of Human Genetics · doi:10.1086/321974 · Cited by 228 · see citing works
Analysis of a CGG sequence at the FMR-1 locus in fragile X families and in the general population.
Snow, K., Doud, L. K., Hagerman, R. J., Pergolizzi, R. G., Erster, S. H., & Thibodeau, S. N. (1993) · PubMed · Cited by 226 · see citing works
Vries, B. B. A. D., van den Ouweland, A. M. W., Mohkamsing, S., Duivenvoorden, H. J., Mol, E., Gelsema, K., van Rijn, M., Halley, D. J. J., Sandkuijl, L. A., Oostra, B. A., et al. (1997) · The American Journal of Human Genetics · doi:10.1086/515496 · Cited by 225 · see citing works
Prevalence of the fragile X syndrome in African‐Americans
Crawford, D. C., Meadows, K. L., Newman, J. L., Taft, L. F., Scott, E., Leslie, M., Shubeck, L., Holmgreen, P., Yeargin‐Allsopp, M., Boyle, C. A., et al. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10427 · Cited by 147 · see citing works
Autistic Spectrum Disorder and the Fragile X Premutation
Goodlin‐Jones, B. L., Tassone, F., Gane, L. W., & Hagerman, R. J. (2004) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/00004703-200412000-00002 · Cited by 115 · see citing works
Self-citationSize bias of fragile X premutation alleles in late-onset movement disorders
Jacquemont, S., Leehey, M. A., Hagerman, R. J., Beckett, L. A., & Hagerman, P. J. (2006) · Journal of Medical Genetics · doi:10.1136/jmg.2006.042374 · Cited by 115 · see citing works
Self-citationBailey, D. B., Skinner, D., Davis, A. M., Whitmarsh, I., & Powell, C. M. (2008) · PEDIATRICS · doi:10.1542/peds.2007-0820 · Cited by 114 · see citing works
Screening for fragile X syndrome: a literature review and modelling study
Song, F., Barton, P., Sleightholme, V., Yao, G., & Fry-Smith, A. (2003) · Health Technology Assessment · doi:10.3310/hta7160 · Cited by 112 · see citing works
Fragile X syndrome is less common than previously estimated
Morton, J. E., Bundey, S., Webb, T. P., MacDonald, F., Rindl, P. M., & Bullock, S. (1997) · Journal of Medical Genetics · doi:10.1136/jmg.34.1.1 · Cited by 92 · see citing works
Newborn Screening for Developmental Disabilities: Reframing Presumptive Benefit
Bailey, D. B., Skinner, D., & Warren, S. F. (2005) · American Journal of Public Health · doi:10.2105/ajph.2004.051110 · Cited by 81 · see citing works
Fragile X–Associated Tremor/Ataxia Syndrome
Amiri, K. M. A., Hagerman, R. J., & Hagerman, P. J. (2008) · Archives of Neurology · doi:10.1001/archneurol.2007.30 · Cited by 73 · see citing works
Self-citationNewborn screening for fragile X syndrome
Bailey, D. B. (2004) · Mental Retardation and Developmental Disabilities Research Reviews · doi:10.1002/mrdd.20002 · Cited by 64 · see citing works
Changing perspectives on the benefits of newborn screening
Bailey, D. B., Beskow, L. M., Davis, A. M., et al. (2006) · Mental Retardation and Developmental Disabilities Research Reviews · doi:10.1002/mrdd.20119 · Cited by 63 · see citing works
Fragile X-associated tremor/ataxia syndrome—an older face of the fragile X gene
Hagerman, P. J., & Hagerman, R. J. (2007) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0373 · Cited by 60 · see citing works
Self-citationTzeng, C., Tsai, L., Hwu, W., Lin, S., Chao, M., Jong, Y., Chu, S., Chao, W.-C., & Lu, C. (2005) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30528 · Cited by 58 · see citing works
Incidence of Fragile X in 5,000 Consecutive Newborn Males
Rife, M. F., Bádenas, C., Mallolas, J., Jiménez, L., Cervera, R., Maya, A. C. L., Glover, G., Rivera, F., & Milà, M. (2003) · Genetic Testing · doi:10.1089/109065703322783725 · Cited by 56 · see citing works
Dawson, A., Chodirker, B. N., & Chudley, A. E. (1995) · Biochemical and Molecular Medicine · doi:10.1006/bmme.1995.1057 · Cited by 49 · see citing works
Spencer, K. (2000) · Prenatal Diagnosis · doi:10.1002/1097-0223(200008)20:8 · Cited by 37 · see citing works
Cosmetic Therapies in Obstetrics and Gynecology Practice: Putting a Toe in the Water?
Laube, D. W. (2008) · Obstetrics and Gynecology · doi:10.1097/gim.0b013e3181862a76 · Cited by 35 · see citing works
Fragile X premutations and (TA)n estrogen receptor polymorphism in women with ovarian dysfunction
Syrrou, M., Georgiou, I. A., Patsalis, P. C., Bouba, I., Adonakis, G., & Pagoulatos, G. N. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19990528)84:3 · Cited by 33 · see citing works
FXTAS: A progressive neurologic syndrome associated with fragile X premutation
Willemsen, R., Mientjes, E., & Oostra, B. A. (2005) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-005-0065-5 · Cited by 30 · see citing works
Mil, M. D., Kruyer, H., Glover, G., S�nchez, A., Carbonell, P., Castellv�-Bel, S., Volpini, V., Rosell, J., Gabarr�n, J., L�pez, I., et al. (1994) · Human Genetics · doi:10.1007/bf00201600 · Cited by 26 · see citing works
Long‐term potentiation in the hippocampus of fragile X knockout mice
Godfraind, J., Reyniers, E., Boulle, K. D., D’Hooge, R., Deyn, P. P. D., Bakker, C. E., Oostra, B. A., Kooy, R. F., & Willems, P. J. (1996) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19960809)64:2 · Cited by 16 · see citing works
Variation of the CGG Repeat in FMR-1 Gene in Normal and Fragile X Chinese Subjects
Chen, T. A., Lu, X., Che, P. K., et al. (1997) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/000456329703400504 · Cited by 13 · see citing works
Wang, Y., Li, C., Lin, M., et al. (2000) · PubMed · Cited by 5 · see citing works
Miller (1999) · doi:10.1002/(sici)1096-8628(19990402)83:4
Turner (1996) · doi:10.1002/(sici)1096-8628(19960712)64:1
Flagged first, then by citations
Research works printed but not linked: 5
- Pesso R, Berkenstadt M, Cuckle H, Gak E, Peleg L, Frydman M, Barkai G: Screening for fragile X syndrome in women of reproductive age. Prenat Diagn 2000, 20:611-614
- Allingham-Hawkins DJ, Babul-Hirji R, Chitayat D, Holden JA, Yang KT, Lee C, Hudson R, Gorwill H, Nolin SL, Glicksman A, Jenkins EC, Brown WT, Howard-Peebles PN, Becchi C, Cummings E, Fallon L, Seitz S, Black SH, Vianna-Morgante AM, Costa SS, Otto PA, Mingroni- Netto RC, Murray A, Webb J, MacSwinney F, Dennis N, Jacobs PA, Syrrou M, Georgiou I, Patsalis PC, Giovannucci Uzielli ML, Guarducci S, Lapi E, Cecconi A, Ricci U, Ricotti G, Biondi C, Scarselli B, Vieri F: Fragile X premutation is a significant risk factor for premature ovarian failure: the international collaborative POF in fragile X study-prelim- inary data. Am J Med Genet 1999, 83:322-325
- Patsalis PC, Sismani C, Hettinger JA, Boumba I, Georgiou I, Stylianidou G, Anastasiadou V, Koukoulli R, Pagoulatos G, Syrrou M: Molecular screening of fragile X (FRAXA) and FRAXE mental retardation syn- dromes in the Hellenic population of Greece and Cyprus: inci- dence, genetic variation, and stability. Am J Med Genet 1999, 84:184 -190
- Holden JJ, Chalifoux M, Wing M, Julien-Inalsingh C, White BN: A rapid, reliable, and inexpensive method for detection of di-and trinucleotide repeat markers and disease loci from dried blood spots. Am J Med Genet 1996, 64:313-318
- Saul RA, Friez M, Eaves K, Stapleton GA, Collins JS, Schwartz CE, and Stevenson RE: Fragile X syndrome detection in newborns-pilot study. Genet Med 2008, 10:714 -719
Cited by
Sorted by citations
Hagerman, R. J., Berry-Kravis, E., Hazlett, H. C., Bailey, D. B., Moine, H., Kooy, R. F., Tassone, F., Gantois, I., Sonenberg, N., Mandel, J. L., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.65 · Cited by 838 · see citing works
Self-citationIncidence of Fragile X Syndrome by Newborn Screening for Methylated FMR1 DNA
Coffee, B., Keith, K., Albizua, I., Malone, T., Mowrey, J., Sherman, S. L., & Warren, S. T. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.09.007 · Cited by 436 · see citing works
Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics
Bagni, C., Tassone, F., Neri, G., & Hagerman, R. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63141 · Cited by 321 · see citing works
Self-citationCordeiro, L., Ballinger, E., Hagerman, R., & Hessl, D. (2011) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-010-9067-y · Cited by 316 · see citing works
Fragile X: Leading the Way for Targeted Treatments in Autism
Wang, L. W., Berry-Kravis, E., & Hagerman, R. J. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.05.005 · Cited by 176 · see citing works
Chonchaiya, W., Au, J., Schneider, A., Hessl, D., Harris, S. W., Laird, M., Mu, Y., Tassone, F., Nguyen, D. V., & Hagerman, R. J. (2012) · Human Genetics · doi:10.1007/s00439-011-1106-6 · Cited by 109 · see citing works
Self-citationUtari, A., Chonchaiya, W., Rivera, S. M., Schneider, A., Hagerman, R. J., Faradz, S. M. H., Ethell, I. M., & Nguyen, D. V. (2010) · American Journal on Intellectual and Developmental Disabilities · doi:10.1352/1944-7558-115.5.433 · Cited by 105 · see citing works
Klusek, J., Martin, G. E., & Losh, M. (2014) · Journal of Intellectual Disability Research · doi:10.1111/jir.12121 · Cited by 99 · see citing works
“FXS occurs in 1 in 2500 individuals (Hagerman 2008; Fernandez-Carvajal et al. 2009) and is caused by a mutation in the Fragile X Mental Retardation 1 (FMR1) gene.”
FMR1 premutation and full mutation molecular mechanisms related to autism
Hagerman, R., Au, J., & Hagerman, P. (2011) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-011-9084-5 · Cited by 85 · see citing works
Self-citation
- Authors
- Fernandez-Carvajal, I., Walichiewicz, P., Xiaosen, X., Pan, R., Hagerman, P. J., & Tassone, F.
- Affiliations
- University of California, Davis (US)
- University of California Davis Medical Center (US)
- Universidad de Valladolid (ES)
- Corresponding author
- Tassone, Flora
- Venue
- The Journal of Molecular Diagnostics
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 11
- Issue
- 4
- Pages
- 324-329
- ISSN
- 1525-1578 (ISSN-L)
- PMC
- PMC2710709
- OpenAlex
- W2032687048
- Cited by
- 204
- References
- 40
- Citations by year
- 2026: 3 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 9 · 2020: 8 · 2019: 5 · 2018: 6 · 2017: 12 · 2016: 10 · 2015: 5 · 2014: 17 · 2013: 21 · 2012: 22
- FWCI
- 18.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Molecular Diagnostics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Universidad de Valladolid
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD040661, HD040661, P30HD002274, 265 HD02274)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- fragile X syndrome, FMR1 gene, CGG repeat expansion, premutation, full mutation, newborn screening, allele frequency, blood spots, intellectual disability, northwest Spain
- MeSH terms
- Alleles, DNA Mutational Analysis, Female, Fragile X Syndrome, Genetic Testing, Humans, Infant, Newborn, Male, Spain, Trinucleotide Repeat Expansion, White People, Fragile X Messenger Ribonucleoprotein 1
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
