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          Institute: MPI für molekulare Genetik     Collection: Department of Human Molecular Genetics     Display Documents

ID: 307322.0, MPI für molekulare Genetik / Department of Human Molecular Genetics
Evidence for a new contiguous gene syndrome, the chromosome 16p13.3 deletion syndrome alias severe Rubinstein–Taybi syndrome
Authors:Bartsch, Oliver; Rasi, Sasan; Delicado, Alicia; Dyack, Sarah; Neumann, Luitgard M.; Seemanová, Eva; Volleth, Marianne; Haaf, Thomas; Kalscheuer, Vera M.
Date of Publication (YYYY-MM-DD):2006-06-17
Title of Journal:Human Genetics
Journal Abbrev.:Hum. Genet.
Issue / Number:3
Start Page:179
End Page:186
Copyright:© Springer. Part of Springer Science+Business Media
Review Status:not specified
Audience:Experts Only
Abstract / Description:Rubinstein–Taybi syndrome (RSTS) is a well-known autosomal dominant mental retardation syndrome with typical facial and skeletal abnormalities. Previously, we have reported two patients presenting with RSTS and additional clinical features including failure to thrive, seizures, and intractable infections (Bartsch et al. in Eur J Hum Genet 7:748–756, 1999). Recently we identified a third patient with this condition, termed here severe RSTS, or chromosome 16p13.3 deletion syndrome. The three patients died in infancy, and all displayed a specific mutation, a chromosomal microdeletion including the 3′-end of the CREBBP gene. Using fluorescence in situ hybridization and closely spaced DNA probes, we characterized the deletion intervals in these patients and in three individuals with a deletion of CREBBP and typical RSTS. The deleted DNA segments were found to greatly vary in size, spanning from ∼40 kb to >3 Mb. Four individuals, including the patients with severe RSTS, exhibited deletions containing gene/s in addition to CREBBP. The patients with severe RSTS all had deletions comprising telomeric neighbor genes of CREBBP, including DNASE1, a dominant gene encoding a nuclease that has been associated with systemic lupus erythematodes. Our findings suggest that severe RSTS is distinct from RSTS and represents a novel true contiguous gene syndrome (chromosome 16p13.3 deletion syndrome). Because of the risk of critical infections and high mortality rate, we recommend that the size of the deletion interval should be determined in CREBBP deletion-positive patients with RSTS, especially in young children. Further studies are needed to delineate the clinical spectrum of the new disorder and to clarify the role of DNASE1.
External Publication Status:published
Document Type:Article
Communicated by:Hans-Hilger Ropers
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Institute for Human Genetics, Mainz University School of Medicine, 55101 Mainz, Germany;
2.Genética Médica, Hospital Universitario “La Paz”, 28046 Madrid, Spain;
3.IWK Health Centre, Dalhousie University, Halifax, NS, Canada, B3K 6R8;
4.Institute of Human Genetics, Charité Campus Virchow-Klinikum, 13353 Berlin, Germany;
5.Institute of Medical Biology and Genetics, 2nd Medical School, Charles University, 15006 Prague 5, Czech Republic;
6.Institute for Human Genetics, Otto von Guericke University, 39120 Magdeburg, Germany.
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