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


ABSTRACT: 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.We report the molecular and/or clinical characterisation 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 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)).Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.

SUBMITTER: Koolen DA 

PROVIDER: S-EPMC3071570 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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

Koolen D A DA   Sharp A J AJ   Hurst J A JA   Firth H V HV   Knight S J L SJ   Goldenberg A A   Saugier-Veber P P   Pfundt R R   Vissers L E L M LE   Destrée A A   Grisart B B   Rooms L L   Van der Aa N N   Field M M   Hackett A A   Bell K K   Nowaczyk M J M MJ   Mancini G M S GM   Poddighe P J PJ   Schwartz C E CE   Rossi E E   De Gregori M M   Antonacci-Fulton L L LL   McLellan M D MD   Garrett J M JM   Wiechert M A MA   Miner T L TL   Crosby S S   Ciccone R R   Willatt L L   Rauch A A   Zenker M M   Aradhya S S   Manning M A MA   Strom T M TM   Wagenstaller J J   Krepischi-Santos A C AC   Vianna-Morgante A M AM   Rosenberg C C   Price S M SM   Stewart H H   Shaw-Smith C C   Brunner H G HG   Wilkie A O M AO   Veltman J A JA   Zuffardi O O   Eichler E E EE   de Vries B B A BB  

Journal of medical genetics 20080715 11


<h4>Background</h4>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.<h4>Aim</h4>We report the molecular and/or clinical characterisation of 22 individuals with the 17q21.31 microdeletion syndrome.<h4>Results</h4>We estimate the prevalence of the syndrome to be 1 in 16,000 and show that it is highly underdiagnosed. Extensive clinical examination revea  ...[more]

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