Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. Issue 11 (15th July 2008)

• Record Type: Journal Article
• Authors: Koolen, D A; Sharp, A J; Hurst, J A; Firth, H V; Knight, S J L; Goldenberg, A; Saugier-Veber, P; Pfundt, R; Vissers, L E L M; Destrée, A; Grisart, B; Rooms, L; Van der Aa, N; Field, M; Hackett, A; Bell, K; Nowaczyk, M J M; Mancini, G M S; Poddighe, P J; Schwartz, C E; Rossi, E; De Gregori, M; Antonacci-Fulton, L L; McLellan, M D; Garrett, J M; Wiechert, M A; Miner, T L; Crosby, S; Ciccone, R; Willatt, L; Rauch, A; Zenker, M; Aradhya, S; Manning, M A; 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 M; Veltman, J A; Zuffardi, O; Eichler, E E; de Vries, B B A;
• Is Part Of: Journal of medical genetics. Volume 45:Issue 11(2008)
• Page Start: 710
• Page End: 720
• Publication Date: 2008-07-15
• Subjects: Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2008.058701
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : 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 (chr17: 41046729–41470954, hg17) encompassing at least six genes, among which is 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 ). Conclusion: Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.