title: Clinical and molecular delineation of the 17q21.31 microdeletion syndrome.
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.
  
  
  OBJECTIVE
  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)).
  
  
  CONCLUSIONS
  Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.
authors.affiliation: Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
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mesh_terms: D000015:Abnormalities, Multiple / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D007446:Chromosome Inversion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002658:Developmental Disabilities / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D005145:Face / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009123:Muscle Hypotonia / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D055815:Young Adult; D016875:tau Proteins
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins