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Cited by 331Down syndrome and intellectual disability researchGenomic variations and chromosomal abnormalitiesGenetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Genotype-phenotype correlations in down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21

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Lyle, Robert, Béna, Frédérique, Gagos, Sarantis, Gehrig, Corinne, Lopez, Gipsy, Schinzel, Albert, Lespinasse, James, Bottani, Armand +20 more·2009·European Journal of Human Genetics
DOI 10.1038/ejhg.2008.214PMC PMC2986205
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Abstract

Down syndrome (DS) is one of the most frequent congenital birth defects, and the most common genetic cause of mental retardation. In most cases, DS results from the presence of an extra copy of chromosome 21. DS has a complex phenotype, and a major goal of DS research is to identify genotype-phenotype correlations. Cases of partial trisomy 21 and other HSA21 rearrangements associated with DS features could identify genomic regions associated with specific phenotypes. We have developed a BAC array spanning HSA21q and used array comparative genome hybridization (aCGH) to enable high-resolution mapping of pathogenic partial aneuploidies and unbalanced translocations involving HSA21. We report the identification and mapping of 30 pathogenic chromosomal aberrations of HSA21 consisting of 19 partial trisomies and 11 partial monosomies for different segments of HSA21. The breakpoints have been mapped to within approximately 85 kb. The majority of the breakpoints (26 of 30) for the partial aneuploidies map within a 10-Mb region. Our data argue against a single DS critical region. We identify susceptibility regions for 25 phenotypes for DS and 27 regions for monosomy 21. However, most of these regions are still broad, and more cases are needed to narrow down the phenotypic maps to a reasonable number of candidate genomic elements per phenotype.

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  • A targeted gene or set of genes hypothesized to have a major influence on a phenotype due to overexpression in DS may be a therapeutic focus.

    “Alternatively, a targeted gene or set of genes hypothesized to have a major influence on a phenotype due to overexpression in DS may be a therapeutic focus (Korbel et al., 2009; Lyle et al., 2009).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Lyle et al., 2009

    The Introduction and Genotype–phenotype correlations section say that identifying chromosome 21 genes or small regions contributing to specific Down syndrome phenotypes is a goal of the research. They do not propose targeting those genes as a therapeutic approach or establish that overexpression of a particular gene or set of genes has a major influence on a phenotype. (LLM, conf=0.84)

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Authors
Lyle, R., Béna, F., Gagos, S., Gehrig, C., Lopez, G., Schinzel, A., Lespinasse, J., Bottani, A., Dahoun, S., Taine, L., Doco-Fenzy, M., Cornillet-Lefèbvre, P., Pelet, A., Lyonnet, S., Toutain, A., Colleaux, L., Horst, J., Kennerknecht, I., Wakamatsu, N., Descartes, M., Franklin, J. C., Florentin-Arar, L., Kitsiou, S., Aït Yahya-Graison, E., Costantine, M., Sinet, P.-M., Delabar, J. M., & Antonarakis, S. E.
Affiliations
  • University of Geneva (CH)
  • Centre Hospitalier Universitaire de Bordeaux (FR)
  • Hôpital Necker-Enfants Malades (FR)
  • Centre Hospitalier Universitaire de Tours (FR)
  • University of Münster (DE)
  • Institute for Developmental Research (JP)
  • University of Alabama at Birmingham (US)
  • National and Kapodistrian University of Athens (GR)
  • Université Paris Diderot (FR)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
  • Lyle, Robert
  • Antonarakis, Stylianos E
ORCID
Venue
European Journal of Human Genetics
Publisher
Springer Science and Business Media LLC
Published
2008-11-12
Volume
17
Issue
4
Pages
454-466
ISSN
  • 1018-4813 (ISSN-L)
  • 1476-5438
DOI
10.1038/ejhg.2008.214
PMC
PMC2986205
OpenAlex
W2085790004
Cited by
331
References
51
Citations by year
2026: 5 · 2025: 8 · 2024: 19 · 2023: 13 · 2022: 15 · 2021: 24 · 2020: 48 · 2019: 14 · 2018: 11 · 2017: 16 · 2016: 22 · 2015: 19 · 2014: 19 · 2013: 14 · 2012: 20
FWCI
21.20
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • European Journal of Human Genetics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • National Science Foundation
  • European Commission
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Keywords
Down syndrome, partial trisomy 21, genotype-phenotype correlation, breakpoint mapping, critical region, unbalanced translocation, BAC array
MeSH terms
Abnormalities, Multiple, Chromosome Deletion, Chromosomes, Human, Pair 21, Down Syndrome, Genotype, Humans, Phenotype, Trisomy, Comparative Genomic Hybridization

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