TY - JOUR T1 - Clinical and molecular delineation of the 17q21.31 microdeletion syndrome JF - Journal of Medical Genetics JO - J Med Genet SP - 710 LP - 720 DO - 10.1136/jmg.2008.058701 VL - 45 IS - 11 AU - D A Koolen AU - A J Sharp AU - J A Hurst AU - H V Firth AU - S J L Knight AU - A Goldenberg AU - P Saugier-Veber AU - R Pfundt AU - L E L M Vissers AU - A Destrée AU - B Grisart AU - L Rooms AU - N Van der Aa AU - M Field AU - A Hackett AU - K Bell AU - M J M Nowaczyk AU - G M S Mancini AU - P J Poddighe AU - C E Schwartz AU - E Rossi AU - M De Gregori AU - L L Antonacci-Fulton AU - M D McLellan II AU - J M Garrett AU - M A Wiechert AU - T L Miner AU - S Crosby AU - R Ciccone AU - L Willatt AU - A Rauch AU - M Zenker AU - S Aradhya AU - M A Manning AU - T M Strom AU - J Wagenstaller AU - A C Krepischi-Santos AU - A M Vianna-Morgante AU - C Rosenberg AU - S M Price AU - H Stewart AU - C Shaw-Smith AU - H G Brunner AU - A O M Wilkie AU - J A Veltman AU - O Zuffardi AU - E E Eichler AU - B B A de Vries Y1 - 2008/11/01 UR - http://jmg.bmj.com/content/45/11/710.abstract N2 - 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. ER -