Cited by 87Genomic variations and chromosomal abnormalitiesGenetics and Neurodevelopmental DisordersGenetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination

Open access
Vandewalle, Joke, Van Esch, Hilde, Govaerts, Karen, Verbeeck, Jelle, Zweier, Christiane, Madrigal, Irene, Mila, Montserrat, Pijkels, Elly +7 more·2009·The American Journal of Human Genetics

Abstract

We report on the identification of a 0.3 Mb inherited recurrent but variable copy-number gain at Xq28 in affected males of four unrelated families with X-linked mental retardation (MR). All aberrations segregate with the disease in the families, and the carrier mothers show nonrandom X chromosome inactivation. Tiling Xq28-region-specific oligo array revealed that all aberrations start at the beginning of the low copy repeat LCR-K1, at position 153.20 Mb, and end just distal to LCR-L2, at 153.54 Mb. The copy-number gain always includes 18 annotated genes, of which RPL10, ATP6AP1 and GDI1 are highly expressed in brain. From these, GDI1 is the most likely candidate gene. Its copy number correlates with the severity of clinical features, because it is duplicated in one family with nonsyndromic moderate MR, is triplicated in males from two families with mild MR and additional features, and is present in five copies in a fourth family with a severe syndromic form of MR. Moreover, expression analysis revealed copy-number-dependent increased mRNA levels in affected patients compared to control individuals. Interestingly, analysis of the breakpoint regions suggests a recombination mechanism that involves two adjacent but different sets of low copy repeats. Taken together, our data strongly suggest that an increased expression of GDI1 results in impaired cognition in a dosage-dependent manner. Moreover, these data also imply that a copy-number gain of an individual gene present in the larger genomic aberration that leads to the severe MECP2 duplication syndrome can of itself result in a clinical phenotype as well.

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 · 10.1016/j.ajhg.2009.10.019

Cites

35 of 35 references verified0 citation errors · 0 not checkable

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?

  • Two unrelated males harbored Xq28 duplications, one de novo and one maternal, corresponding to a ∼0.3 Mb segmental-duplication-mediated gain (153.2-153.5 Mb), previously reported in X-linked ID.

    “For example, two unrelated males were found to harbor Xq28 duplications (MIM 300815), one de novo and one maternal, corresponding to a ∼0.3 Mb segmental-duplication-mediated gain (153.2–153.5 Mb), which was previously reported in X-linked ID.42”

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

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Vandewalle, J., Van Esch, H., Govaerts, K., Verbeeck, J., Zweier, C., Madrigal, I., Mila, M., Pijkels, E., Fernandez, I., Kohlhase, J., Spaich, C., Rauch, A., Fryns, J.-P., Marynen, P., & Froyen, G.
Affiliations
  • Vlaams Instituut voor Biotechnologie (BE)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • Hospital Clínic de Barcelona (ES)
  • Universitair Ziekenhuis Leuven (BE)
  • Universidad de Valladolid (ES)
  • University of Freiburg (DE)
  • Olgahospital (DE)
Corresponding author
Froyen, Guy
Venue
The American Journal of Human Genetics
Publisher
Elsevier BV
Published
2009-12
Volume
85
Issue
6
Pages
809-822
ISSN
0002-9297 (ISSN-L)
OpenAlex
W1990251817
Cited by
86
References
35
Citations by year
2026: 2 · 2025: 4 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 5 · 2015: 4 · 2014: 9 · 2013: 9 · 2012: 8
FWCI
4.07
Type
journal article
Language
en
Open access
Locations
  • The American Journal of Human Genetics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Lirias (submittedVersion, other-oa)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
  • Fonds Wetenschappelijk Onderzoek
  • Vlaamse regering
  • Instituto de Salud Carlos III
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Keywords
X-linked intellectual disability, GDI1, segmental duplication, recombination mechanisms, X chromosome inactivation, MECP2 duplication syndrome, ribosomal protein L10, ATP6AP1, gene dosage, mRNA expression
MeSH terms
Adult, Brain, Child, Child, Preschool, Chromosome Aberrations, Chromosome Mapping, Female, Humans, Male, Intellectual Disability, Models, Genetic, Nucleic Acid Hybridization, Pedigree, Phenotype, Recombination, Genetic, Gene Dosage, Chromosomes, Human, X

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