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Koolen, D.A.* ; Sharp, A.J.* ; Hurst, J.A.* ; Firth, H.V.* ; Knight, S.J.* ; Goldenberg, A.* ; Saugier-Veber, P.* ; Pfundt, R.* ; Vissers, L.E.* ; Destrée, A.* ; Grisart, B.* ; Rooms, L.* ; van der Aa, N.* ; Field, M.* ; Hackett, A.* ; Bell, K.* ; Nowaczyk, M.J.* ; Mancini, G.M.* ; Poddighe, P.J.* ; Schwartz, C.E.* ; Rossi, E.* ; De, Gregori, M.* ; Antonacci-Fulton, L.L.* ; McLellan, M.D., II* ; Garrett, J.M.* ; Wiechert, M.A.* ; Miner, T.L.* ; Crosby, S.* ; Ciccone, R.* ; Willatt, L.* ; Rauch, A.* ; Zenker, M.* ; Aradhya, S.* ; Manning, MA.* ; Strom, T.M. ; Wagenstaller, J. ; Krepischi-Santos, A.C.* ; Vianna-Morgante, A.M.* ; Rosenberg, C.* ; Price, S.M.* ; Stewart, H.* ; Shaw-Smith, C.* ; Brunner, H.G.* ; Wilkie, A.O.* ; Veltman, J.A.* ; Zuffardi, O.* ; Eichler, E.E.* ; de, Vries, B.B.*

Clinical and molecular delineation of the 17q21.31 microdeletion syndrome.

J. Med. Genet. 45, 710-720 (2008)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The chromosome 17q21.31 microdeletion syndrome is a novel genomic disorder that has originally been identified using high-resolution genome analyses in patients with unexplained mental retardation. Here we report the molecular and/or clinical characterization of 22 individuals with the 17q21.31 microdeletion syndrome. We estimate the prevalence of the syndrome to be 1 in 16,000 and show that it is highly underdiagnosed. Extensive clinical examination, reveals that developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behavior are the most characteristic features. Other clinically important features include epilepsy, heart defects (ASD, VSD), and kidney/ urologic anomalies. Using high-resolution oligonucleotide arrays, we narrow the 17q21.31 critical region to a 424-kb genomic segment (chr17: 41046729-41470954, hg17), encompassing at least six genes, among which the gene encoding microtubule-associated protein tau (MAPT). Mutation screening of MAPT in 122 individuals with a phenotype suggestive of 17q21.31 deletion carriers, but who do not carry the recurrent deletion, failed to identify any disease-associated variants. In five deletion carriers, we identify a <500-bp rearrangement hotspot at the proximal breakpoint contained within an L2 LINE motif and show that in every case examined, the parent originating the deletion carries a common 900-kb 17q21.31 inversion polymorphism, indicating that this inversion is a necessary factor for deletion to occur (p<10-5). Our data establishes the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognizable genomic disorder.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 0022-2593
e-ISSN 1468-6244
Zeitschrift Journal of Medical Genetics
Quellenangaben Band: 45, Heft: 11, Seiten: 710-720 Artikelnummer: , Supplement: ,
Verlag BMJ Publishing Group
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)