Two high throughput technologies to detect segmental aneuploidies identify new Williams-Beuren syndrome patients with atypical deletions
Open accessAbstract
Objective: To develop and compare two new technologies for diagnosing a contiguous gene syndrome, the Williams-Beuren syndrome (WBS). Methods: The first proposed method, named paralogous sequence quantification (PSQ), is based on the use of paralogous sequences located on different chromosomes and quantification of specific mismatches present at these loci using pyrosequencing technology. The second exploits quantitative real time polymerase chain reaction (QPCR) to assess the relative quantity of an analysed locus. Results: A correct and unambiguous diagnosis was obtained for 100% of the analysed samples with either technique (n = 165 and n = 155, respectively). These methods allowed the identification of two patients with atypical deletions in a cohort of 182 WBS patients. Both patients presented with mild facial anomalies, mild mental retardation with impaired visuospatial cognition, supravalvar aortic stenosis, and normal growth indices. These observations are consistent with the involvement of GTF2IRD1 or GTF2I in some of the WBS facial features. Conclusions: Both PSQ and QPCR are robust, easy to interpret, and simple to set up. They represent a competitive alternative for the diagnosis of segmental aneuploidies in clinical laboratories. They have advantages over fluorescence in situ hybridisation or microsatellites/SNP genotyping for detecting short segmental aneuploidies as the former is costly and labour intensive while the latter depends on the informativeness of the polymorphisms.
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?
People with atypical deletions and varying degrees of craniofacial abnormalities implicate both proximal and distal ends of the deletion, suggesting that more than one gene is responsible.
“People with atypical deletions, and varying degrees of craniofacial abnormalities, implicate both proximal and distal ends of the deletion, suggesting that more than one gene is responsible [36-41].”
From A genome-wide screen for modifiers of transgene variegation identifies genes with critical roles in development (2008) · cites this paper as [40]
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
Initial sequencing and analysis of the human genome
International Human Genome Sequencing Consortium, Whitehead Institute for Biomedical Research, C. F. G. R., Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., Devon, K., Dewar, K., et al. (2001) · Nature · doi:10.1038/35057062 · Cited by 24,216 · see citing works
Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., Van Roy, N., De Paepe, A., & Speleman, F. (2002) · Genome Biology · doi:10.1186/gb-2002-3-7-research0034 · Cited by 20,038 · see citing works
The sequence of the human genome
Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A., et al. (2001) · Science · doi:10.1126/science.1058040 · Cited by 13,909 · see citing works
Finishing the euchromatic sequence of the human genome
International Human Genome Sequencing Consortium (2004) · Nature · doi:10.1038/nature03001 · Cited by 4,971 · see citing works
Kinetic PCR Analysis: Real-time Monitoring of DNA Amplification Reactions
Higuchi, R., Fockler, C., Dollinger, G. D., & Watson, R. H. (1993) · Nature Biotechnology · doi:10.1038/nbt0993-1026 · Cited by 2,165 · see citing works
Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome
Ewart, A. K., Morris, C. A., Atkinson, D., Jin, W., Sternes, K., Spallone, P., Stock, A. D., Leppert, M., & Keating, M. T. (1993) · Nature Genetics · doi:10.1038/ng0993-11 · Cited by 1,138 · see citing works
Simultaneous Amplification and Detection of Specific DNA Sequences
Higuchi, R., Dollinger, G. D., Walsh, P. S., & Griffith, R. L. (1992) · Nature Biotechnology · doi:10.1038/nbt0492-413 · Cited by 1,130 · see citing works
Prevalence Estimation of Williams Syndrome
Strømme, P., Bjømstad, P. G., & Ramstad, K. (2002) · Journal of Child Neurology · doi:10.1177/088307380201700406 · Cited by 779 · see citing works
Chromosome 21 and Down syndrome: from genomics to pathophysiology
Antonarakis, S. E., Lyle, R., Dermitzakis, E. T., Reymond, A., & Deutsch, S. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1448 · Cited by 703 · see citing works
Self-citationNatural history of Williams syndrome: Physical characteristics
Morris, C. A., Demsey, S. A., Leonard, C. O., Dilts, C., & Blackburn, B. L. (1988) · The Journal of Pediatrics · doi:10.1016/s0022-3476(88)80272-5 · Cited by 670 · see citing works
Neuropsychological, neurological, and neuroanatomical profile of Williams syndrome
Bellugi, U., Bihrle, A. M., Jernigan, T. L., Trauner, D., & Doherty, S. (2005) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320370621 · Cited by 423 · see citing works
Mutational Mechanisms of Williams-Beuren Syndrome Deletions
Bayés, M., Magano, L. F., Rivera, N. F., Flores, R., & Jurado, L. A. P. (2003) · The American Journal of Human Genetics · doi:10.1086/376565 · Cited by 337 · see citing works
Lowery, M. C., Morris, C. A., Ewart, A. K., Brothman, L. J., Zhu, X., Leonard, C. O., Carey, J. C., Keating, M. T., & Brothman, A. R. (1995) · PubMed Central · Cited by 307 · see citing works
VI. Genome structure and cognitive map of Williams syndrome
Korenberg, J. R., Chen, X.-N., Hirota, H., Lai, Z., Bellugi, U., Burian, D., Roe, B., & Matsuoka, R. (2000) · Journal of Cognitive Neuroscience · doi:10.1162/089892900562002 · Cited by 285 · see citing works
Multisystem study of 20 older adults with Williams syndrome
Cherniske, E. M., Carpenter, T. O., Klaiman, C., Young, E., Bregman, J. D., Insogna, K. L., Schultz, R. T., & Pober, B. R. (2004) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30400 · Cited by 246 · see citing works
Tassabehji, M., Metcalfe, K., Karmiloff‐Smith, A., Carette, M. J. M., Grant, J., Dennis, N. R., Reardon, W., Splitt, M. P., Read, A., & Donnai, D. (1999) · The American Journal of Human Genetics · doi:10.1086/302214 · Cited by 241 · see citing works
Williams-Beuren syndrome:genes and mechanisms
Francke, U. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.10.1947 · Cited by 238 · see citing works
Williams-Beuren syndrome: a challenge for genotype-phenotype correlations
Tassabehji, M. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg299 · Cited by 188 · see citing works
Morris, C. A., Mervis, C. Β., Hobart, H. H., Gregg, R. G., Bertrand, J., Ensing, G. J., Sommer, A., Moore, C. A., Hopkin, R. J., Spallone, P., et al. (2003) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.20496 · Cited by 185 · see citing works
Identification of additional transcripts in the Williams-Beuren syndrome critical region
Merla, G., Ucla, C., Guipponi, M., et al. (2002) · Human Genetics · doi:10.1007/s00439-002-0710-x · Cited by 131 · see citing works
Self-citationHirota, H., Matsuoka, R., Chen, X.-N., Salandanan, L. S., Lincoln, A., Rose, F. E., Sunahara, M., Osawa, M., Bellugi, U., & Korenberg, J. R. (2003) · Genetics in Medicine · doi:10.1097/01.gim.0000076975.10224.67 · Cited by 123 · see citing works
Valero, M. C., de Luis, O., Cruces, J., & Jurado, L. A. P. (2000) · Genomics · doi:10.1006/geno.2000.6312 · Cited by 105 · see citing works
Using case study comparisons to explore genotype-phenotype correlations in Williams-Beuren syndrome
Karmiloff‐Smith, A., Grant, J., Ewing, S., Carette, M. J. M., Metcalfe, K., Donnai, D., Read, A., & Tassabehji, M. (2003) · Journal of Medical Genetics · doi:10.1136/jmg.40.2.136 · Cited by 96 · see citing works
Botta, A., Novelli, G., Mari, A., Novelli, A., Sabani, M., Korenberg, J. R., Osborne, L. R., Digilio, M. C., Giannotti, A., & Dallapiccola, B. (1999) · Journal of Medical Genetics · doi:10.1136/jmg.36.6.478 · Cited by 93 · see citing works
Self-citationQuantitative PCR genotyping assay for the Ts65Dn mouse model of Down syndrome
Liu, D. P., Schmidt, C., Billings, T., & Davisson, M. T. (2003) · BioTechniques · doi:10.2144/03356st02 · Cited by 84 · see citing works
Williams–Beuren Syndrome: Unraveling the Mysteries of a Microdeletion Disorder
Osborne, L. R. (1999) · Molecular Genetics and Metabolism · doi:10.1006/mgme.1999.2844 · Cited by 77 · see citing works
Gagliardi, C., Bonaglia, M. C., Selicorni, A., Borgatti, R., & Giorda, R. (2003) · Journal of Medical Genetics · doi:10.1136/jmg.40.7.526 · Cited by 77 · see citing works
Partial deletion of the critical 1.5 Mb interval in Williams-Beuren syndrome
Heller, R., Rauch, A. M., Lüttgen, S., Schröder, B., & Winterpacht, A. (2003) · Journal of Medical Genetics · doi:10.1136/jmg.40.8.e99 · Cited by 63 · see citing works
Detection of aneuploidies by paralogous sequence quantification
Deutsch, S., Choudhury, U., Merla, G., Howald, C., Sylvan, A., & Antonarakis, S. E. (2004) · Journal of Medical Genetics · doi:10.1136/jmg.2004.023184 · Cited by 49 · see citing works
Self-citationDuba, H.-C., Doll, A., Neyer, M., Erdel, M., Mann, C., Hammerer, I., Utermann, G., & Grzeschik, K.-H. (2002) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5200812 · Cited by 31 · see citing works
Microsatellite DNA markers detects 95% of chromosome 22q11 deletions.
Bonnet, D., Cormier‐Daire, V., Kachaner, J., et al. (1997) · PubMed · Cited by 30 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Pober, B. R. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0903074 · Cited by 848 · see citing works
Antonell, A., Del Campo, M., Magano, L. F., Kaufmann, L., Martínez de la Iglesia, J., Gallastegui, F., Flores, R., Schweigmann, U., Fauth, C., Kotzot, D., et al. (2010) · Journal of Medical Genetics · doi:10.1136/jmg.2009.071712 · Cited by 163 · see citing works
Ashe, A., Morgan, D. K., Whitelaw, N. C., Bruxner, T. J., Vickaryous, N. K., Cox, L. L., Butterfield, N. C., Wicking, C., Blewitt, M. E., Wilkins, S. J., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-12-r182 · Cited by 117 · see citing works
Edelmann, L., Prosnitz, A., Pardo, S., Bhatt, J., Cohen, N., Lauriat, T., Ouchanov, L., González, P. J., Manghi, E. R., Bondy, P., et al. (2007) · Journal of Medical Genetics · doi:10.1136/jmg.2006.044537 · Cited by 113 · see citing works
Williams syndrome transcription factor is critical for neural crest cell function in Xenopus laevis
Barnett, C., Yazgan, O., Kuo, H.-C., Malakar, S., Thomas, T., Fitzgerald, A., Harbour, W., Henry, J. J., & Krebs, J. E. (2012) · Mechanisms of Development · doi:10.1016/j.mod.2012.06.001 · Cited by 48 · see citing works
- Authors
- Howald, C., Merla, G., Digilio, M. C., Amenta, S., Lyle, R., Deutsch, S., Choudhury, U., Bottani, A., Antonarakis, S. E., Fryssira, H., Dallapiccola, B., & Reymond, A.
- Affiliations
- University of Geneva (CH)
- Bambino Gesù Children's Hospital (IT)
- National and Kapodistrian University of Athens (GR)
- University of Lausanne (CH)
- Corresponding author
- Reymond, A
- ORCID
- Venue
- Journal of Medical Genetics
- Publisher
- BMJ
- Published
- 2005-07-01
- Volume
- 43
- Issue
- 3
- Pages
- 266-273
- ISSN
- 0022-2593 (ISSN-L)
- 1468-6244
- PMC
- PMC2563253
- OpenAlex
- W2110815266
- Cited by
- 72
- References
- 31
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 1 · 2019: 5 · 2018: 2 · 2017: 1 · 2016: 5 · 2015: 6 · 2014: 5 · 2013: 3 · 2012: 6
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Medical Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion)
- Funders
- Fondation Jérôme Lejeune
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- Williams syndrome, segmental aneuploidy, pyrosequencing, quantitative real-time PCR, atypical deletion, GTF2IRD1, GTF2I, contiguous gene syndrome, facial anomalies, intellectual disability, supravalvular aortic stenosis
- MeSH terms
- Aneuploidy, Diagnosis, Differential, Humans, Polymorphism, Genetic, Polymerase Chain Reaction, Sequence Deletion, In Situ Hybridization, Fluorescence, Williams Syndrome
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
