Cited by 361Genomic variations and chromosomal abnormalitiesCongenital limb and hand anomaliesPlatelet Disorders and Treatments

Complex Inheritance Pattern Resembling Autosomal Recessive Inheritance Involving a Microdeletion in Thrombocytopenia–Absent Radius Syndrome

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Klopocki, Eva, Schulze, Harald, Strauß, Gabriele, Ott, Claus-Eric, Hall, Judith, Trotier, Fabienne, Fleischhauer, Silke, Greenhalgh, Lynn +10 more·2007·The American Journal of Human Genetics

Abstract

Thrombocytopenia-absent radius (TAR) syndrome is characterized by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia in the presence of both thumbs. Other frequent associations are congenital heart disease and a high incidence of cow's milk intolerance. Evidence for autosomal recessive inheritance comes from families with several affected individuals born to unaffected parents, but several other observations argue for a more complex pattern of inheritance. In this study, we describe a common interstitial microdeletion of 200 kb on chromosome 1q21.1 in all 30 investigated patients with TAR syndrome, detected by microarray-based comparative genomic hybridization. Analysis of the parents revealed that this deletion occurred de novo in 25% of affected individuals. Intriguingly, inheritance of the deletion along the maternal line as well as the paternal line was observed. The absence of this deletion in a cohort of control individuals argues for a specific role played by the microdeletion in the pathogenesis of TAR syndrome. We hypothesize that TAR syndrome is associated with a deletion on chromosome 1q21.1 but that the phenotype develops only in the presence of an additional as-yet-unknown modifier (mTAR).

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Crossref · 10.1086/510919

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Authors
Klopocki, E., Schulze, H., Strauß, G., Ott, C.-E., Hall, J., Trotier, F., Fleischhauer, S., Greenhalgh, L., Newbury-Ecob, R. A., Neumann, L. M., Habenicht, R., König, R., Seemanova, E., Megarbane, A., Ropers, H.-H., Ullmann, R., Horn, D., & Mundlos, S.
Affiliations
  • Charité – Universitätsmedizin Berlin (DE)
  • University of British Columbia (CA)
  • Bristol Royal Hospital for Children (GB)
  • Katholisches Kinderkrankenhaus Wilhelmstift (DE)
  • University Hospital Frankfurt (DE)
  • Max Planck Institute for Molecular Genetics (DE)
Corresponding author
Mundlos, Stefan
Venue
The American Journal of Human Genetics
Publisher
Elsevier BV
Published
2007-02
Volume
80
Issue
2
Pages
232-240
ISSN
0002-9297 (ISSN-L)
OpenAlex
W2001475328
Cited by
360
References
42
Citations by year
2026: 4 · 2025: 6 · 2024: 5 · 2023: 9 · 2022: 10 · 2021: 16 · 2020: 9 · 2019: 19 · 2018: 9 · 2017: 15 · 2016: 6 · 2015: 22 · 2014: 17 · 2013: 27 · 2012: 30
FWCI
14.70
Type
journal article
Language
en
Open access
Locations
  • The American Journal of Human Genetics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Wellcome Trust
  • Deutsche Forschungsgemeinschaft
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Developmental Biology › Congenital limb and hand anomalies
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
Keywords
thrombocytopenia-absent radius syndrome, autosomal recessive inheritance, radial aplasia, de novo deletion, congenital heart disease, cow's milk intolerance
MeSH terms
Adolescent, Adult, Child, Child, Preschool, Chromosome Deletion, Chromosomes, Human, Pair 1, Female, Humans, Infant, Male, Middle Aged, Radius, Syndrome, Thrombocytopenia, Inheritance Patterns

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