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

D. A. Koolen, A. J. Sharp, J. A. Hurst, H. V. Firth, S. J L Knight, A. Goldenberg, P. Saugier-Veber, R. Pfundt, L. E L M Vissers, A. Destrée, B. Grisart, L. Rooms, N. Van der Aa, M. Field, A. Hackett, K. Bell, M. J M Nowaczyk, G. M S Mancini, P. J. Poddighe, C. E. SchwartzE. Rossi, M. De Gregori, L. L. Antonacci-Fulton, M. D. McLellan, J. M. Garrett, M. A. Wiechert, T. L. Miner, S. Crosby, R. Ciccone, L. Willatt, A. Rauch, M. Zenker, S. Aradhya, M. A. Manning, T. M. Strom, J. Wagenstaller, A. C. Krepischi-Santos, A. M. Vianna-Morgante, C. Rosenberg, S. M. Price, H. Stewart, C. Shaw-Smith, H. G. Brunner, A. O M Wilkie, J. A. Veltman, O. Zuffardi, E. E. Eichler, B. B A de Vries

Research output: Contribution to journalArticle

154 Citations (Scopus)

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 (007: 41046729-41470954, hg17) encompassing at least six genes, among which is the gene encoding microtubule associated protein tau IMAM 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 -5). Conclusion: Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.

Original languageEnglish
Pages (from-to)710-720
Number of pages11
JournalJournal of Medical Genetics
Volume45
Issue number11
DOIs
Publication statusPublished - Nov 2008

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Nose
Pyrus
Muscle Hypotonia
Microtubule-Associated Proteins
Oligonucleotide Array Sequence Analysis
Intellectual Disability
Genes
Epilepsy
Genome
Phenotype
Kidney
Mutation
Chromosome 17q21.31 Deletion Syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Koolen, D. A., Sharp, A. J., Hurst, J. A., Firth, H. V., Knight, S. J. L., Goldenberg, A., ... de Vries, B. B. A. (2008). Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. Journal of Medical Genetics, 45(11), 710-720. https://doi.org/10.1136/jmg.2008.058701

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

In: Journal of Medical Genetics, Vol. 45, No. 11, 11.2008, p. 710-720.

Research output: Contribution to journalArticle

Koolen, DA, Sharp, AJ, Hurst, JA, Firth, HV, Knight, SJL, Goldenberg, A, Saugier-Veber, P, Pfundt, R, Vissers, LELM, Destrée, A, Grisart, B, Rooms, L, Van der Aa, N, Field, M, Hackett, A, Bell, K, Nowaczyk, MJM, 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 2008, 'Clinical and molecular delineation of the 17q21.31 microdeletion syndrome', Journal of Medical Genetics, vol. 45, no. 11, pp. 710-720. https://doi.org/10.1136/jmg.2008.058701
Koolen DA, Sharp AJ, Hurst JA, Firth HV, Knight SJL, Goldenberg A et al. Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. Journal of Medical Genetics. 2008 Nov;45(11):710-720. https://doi.org/10.1136/jmg.2008.058701
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. / Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. In: Journal of Medical Genetics. 2008 ; Vol. 45, No. 11. pp. 710-720.
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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 (007: 41046729-41470954, hg17) encompassing at least six genes, among which is the gene encoding microtubule associated protein tau IMAM 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 -5). Conclusion: Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.",
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TY - JOUR

T1 - Clinical and molecular delineation of the 17q21.31 microdeletion syndrome

AU - Koolen, D. A.

AU - Sharp, A. J.

AU - Hurst, J. A.

AU - Firth, H. V.

AU - Knight, S. J L

AU - Goldenberg, A.

AU - Saugier-Veber, P.

AU - Pfundt, R.

AU - Vissers, L. E L M

AU - Destrée, A.

AU - Grisart, B.

AU - Rooms, L.

AU - Van der Aa, N.

AU - Field, M.

AU - Hackett, A.

AU - Bell, K.

AU - Nowaczyk, M. J M

AU - Mancini, G. M S

AU - Poddighe, P. J.

AU - Schwartz, C. E.

AU - Rossi, E.

AU - De Gregori, M.

AU - Antonacci-Fulton, L. L.

AU - McLellan, M. D.

AU - Garrett, J. M.

AU - Wiechert, M. A.

AU - Miner, T. L.

AU - Crosby, S.

AU - Ciccone, R.

AU - Willatt, L.

AU - Rauch, A.

AU - Zenker, M.

AU - Aradhya, S.

AU - Manning, M. A.

AU - Strom, T. M.

AU - Wagenstaller, J.

AU - Krepischi-Santos, A. C.

AU - Vianna-Morgante, A. M.

AU - Rosenberg, C.

AU - Price, S. M.

AU - Stewart, H.

AU - Shaw-Smith, C.

AU - Brunner, H. G.

AU - Wilkie, A. O M

AU - Veltman, J. A.

AU - Zuffardi, O.

AU - Eichler, E. E.

AU - de Vries, B. B A

PY - 2008/11

Y1 - 2008/11

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 (007: 41046729-41470954, hg17) encompassing at least six genes, among which is the gene encoding microtubule associated protein tau IMAM 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 -5). Conclusion: Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.

AB - 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 (007: 41046729-41470954, hg17) encompassing at least six genes, among which is the gene encoding microtubule associated protein tau IMAM 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 -5). Conclusion: Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.

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