Clinical and molecular delineation of the 17q21.31 microdeletion syndrome Academic Article uri icon

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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.

authors

  • Koolen, DA
  • Sharp, AJ
  • Hurst, JA
  • Firth, HV
  • Knight, SJL
  • Goldenberg, A
  • Saugier-Veber, P
  • Pfundt, R
  • Vissers, LELM
  • Destree, A
  • Grisart, B
  • Rooms, L
  • Van der Aa, N
  • Field, M
  • Hackett, A
  • Bell, Kathleen
  • Nowaczyk, Malgorzata
  • Mancini, GMS
  • Poddighe, PJ
  • Schwartz, CE
  • Rossi, E
  • De Gregori, M
  • Antonacci-Fulton, LL
  • McLellan, MD
  • Garrett, JM
  • Wiechert, MA
  • Miner, TL
  • Crosby, S
  • Ciccone, R
  • Willatt, L
  • Rauch, A
  • Zenker, M
  • Aradhya, S
  • Manning, MA
  • Strom, TM
  • Wagenstaller, J
  • Krepischi-Santos, AC
  • Vianna-Morgante, AM
  • Rosenberg, C
  • Price, SM
  • Stewart, H
  • Shaw-Smith, C
  • Brunner, HG
  • Wilkie, AOM
  • Veltman, JA
  • Zuffardi, O
  • Eichler, EE
  • de Vries, BBA

publication date

  • November 1, 2008

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