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

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

Research output: Contribution to journalArticlepeer-review

180 Scopus citations


Background: 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. Aim: We report the molecular and/or clinical characterisation of 22 individuals with the 17q21.31 microdeletion syndrome. Results: 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 behaviour are the most characteristic features. Other clinically important features include epilepsy, heart defects and kidney/urologic anomalies. Using high resolution oligonucleotide arrays we narrow the 17q21.31 critical region to a 424 kb genomic segment (007: 41046729-41470954, hg17) encompassing at least six genes, among which is the gene encoding microtubule associated protein tau IMAM 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). Conclusion: Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.

Original languageEnglish
Pages (from-to)710-720
Number of pages11
JournalJournal of Medical Genetics
Issue number11
StatePublished - Nov 2008


Dive into the research topics of 'Clinical and molecular delineation of the 17q21.31 microdeletion syndrome'. Together they form a unique fingerprint.

Cite this