Clinical and molecular delineation of the 17q21.31 microdeletion syndrome.
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 1...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2008
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| _version_ | 1797052036937678848 |
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| author | Koolen, D Sharp, A Hurst, J Firth, H Knight, S Goldenberg, A Saugier-Veber, P Pfundt, R Vissers, L Destrée, A Grisart, B Rooms, L Van der Aa, N Field, M Hackett, A Bell, K Nowaczyk, M Mancini, G Poddighe, P Schwartz, C Rossi, E De Gregori, M Antonacci-Fulton, L McLellan, MD Garrett, J |
| author_facet | Koolen, D Sharp, A Hurst, J Firth, H Knight, S Goldenberg, A Saugier-Veber, P Pfundt, R Vissers, L Destrée, A Grisart, B Rooms, L Van der Aa, N Field, M Hackett, A Bell, K Nowaczyk, M Mancini, G Poddighe, P Schwartz, C Rossi, E De Gregori, M Antonacci-Fulton, L McLellan, MD Garrett, J |
| author_sort | Koolen, D |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T18:27:17Z |
| format | Journal article |
| id | oxford-uuid:086504d4-1f86-4092-8ad9-4cdf44f007c2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:27:17Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:086504d4-1f86-4092-8ad9-4cdf44f007c22022-03-26T09:12:46ZClinical and molecular delineation of the 17q21.31 microdeletion syndrome.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:086504d4-1f86-4092-8ad9-4cdf44f007c2EnglishSymplectic Elements at Oxford2008Koolen, DSharp, AHurst, JFirth, HKnight, SGoldenberg, ASaugier-Veber, PPfundt, RVissers, LDestrée, AGrisart, BRooms, LVan der Aa, NField, MHackett, ABell, KNowaczyk, MMancini, GPoddighe, PSchwartz, CRossi, EDe Gregori, MAntonacci-Fulton, LMcLellan, MDGarrett, JBACKGROUND: 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. |
| spellingShingle | Koolen, D Sharp, A Hurst, J Firth, H Knight, S Goldenberg, A Saugier-Veber, P Pfundt, R Vissers, L Destrée, A Grisart, B Rooms, L Van der Aa, N Field, M Hackett, A Bell, K Nowaczyk, M Mancini, G Poddighe, P Schwartz, C Rossi, E De Gregori, M Antonacci-Fulton, L McLellan, MD Garrett, J Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. |
| title | Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. |
| title_full | Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. |
| title_fullStr | Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. |
| title_full_unstemmed | Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. |
| title_short | Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. |
| title_sort | clinical and molecular delineation of the 17q21 31 microdeletion syndrome |
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