| Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. | |
| | |
MedLine Citation:
|
PMID: 18628315 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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:
|
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 Schwartz; E 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 |
Related Documents
:
|
18759095 - Peters plus syndrome. 11152145 - A novel syndrome involving primary skeletal growth and retardation in siblings. 2099765 - Angelman's syndrome in infancy. 1536185 - Syndrome of microcephaly, brachmann-de lange-like facial changes, severe metatarsus add... 6614045 - Eosinophilic fasciitis: a distinct clinical entity? 15150435 - Typical and atypical cogan's syndrome: 32 cases and review of the literature. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-07-15 |
Journal Detail:
|
Title: Journal of medical genetics Volume: 45 ISSN: 1468-6244 ISO Abbreviation: J. Med. Genet. Publication Date: 2008 Nov |
Date Detail:
|
Created Date: 2008-11-03 Completed Date: 2008-12-31 Revised Date: 2011-07-28 |
Medline Journal Info:
|
Nlm Unique ID: 2985087R Medline TA: J Med Genet Country: England |
Other Details:
|
Languages: eng Pagination: 710-20 Citation Subset: IM |
Affiliation:
|
Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Abnormalities, Multiple*
/
epidemiology,
genetics,
physiopathology Adolescent Adult Child Child, Preschool Chromosome Deletion* Chromosome Inversion Chromosomes, Human, Pair 17 / genetics* Developmental Disabilities* / epidemiology, genetics, physiopathology Face / pathology Female Humans Infant Male Muscle Hypotonia / epidemiology, genetics, physiopathology Oligonucleotide Array Sequence Analysis Polymorphism, Single Nucleotide Prevalence Young Adult tau Proteins |
| Grant Support | |
ID/Acronym/Agency:
|
HD043569/HD/NICHD NIH HHS; R01 HD043569-06/HD/NICHD NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
|
0/MAPT protein, human; 0/tau Proteins |
| Comments/Corrections | |
Erratum In:
|
J Med Genet. 2009 Aug;46(8):576 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Alteration of expression of muscle specific isoforms of the fragile X related protein 1 (FXR1P) in f...
Next Document: A phase i study of bolus 5-fluorouracil and leucovorin combined with weekly paclitaxel (FLTAX) as fi...