| Atypical deletion of 22q11.2: detection using the FISH TBX1 probe and molecular characterization with high-density SNP arrays. | |
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MedLine Citation:
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PMID: 19467348 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Despite the heterogeneous clinical presentations, the majority of patients with 22q11.2 deletion syndrome (22q11.2 DS) have either a common recurrent 3 Mb deletion or a less common, 1.5 Mb nested deletion, with breakpoint sites in flanking low-copy repeats (LCR) sequences. Only a small number of atypical deletions have been reported and precisely defined. Haploinsufficiency of the TBX1 gene was determined to be the likely cause of 22q11.2 DS. The diagnostic procedure usually used is FISH using commercially probes (N25 or TUPLE1). However, this test does not contain TBX1, and fails to detect deletions that are either proximal or distal to the FISH probes. Here, we report on two patients with clinical features suggestive of 22q11.2 DS, a male infant with facial dysmorphia, pulmonary atresia, ventricular septal defect, neonatal hypocalcemia, and his affected mother, with facial dysmorphia, learning disabilities, and hypernasal speech. They were tested negative for 22q11.2 DS using N25 or TUPLE1 probes, but were shown deleted for a probe containing TBX1. Delineation of the deletion was performed using high-density SNP arrays (Illumina, 370K). This atypical deletion was spanning 1.89 Mb. The distal breakpoint resided in LCR-D, sharing the same distal breakpoint with the 3 Mb common deletion. The proximal breakpoint was located 105 kb telomeric to TUPLE1, representing a new breakpoint variant that does not correspond to known LCRs of 22q11.2. We conclude that FISH with the TBX1 probe is an accurate diagnostic tool for 22q11.2 DS, with a higher sensitivity than FISH using standard probes, detecting all but the rarest deletions, greatly reducing the false negative rate. |
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Authors:
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Marie-Paule Beaujard; Sandra Chantot; Michèle Dubois; Boris Keren; Wassila Carpentier; Philippe Mabboux; Sandra Whalen; Michel Vodovar; Jean-Pierre Siffroi; Marie-France Portnoï |
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Publication Detail:
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Type: Case Reports; Journal Article Date: 2009-05-23 |
Journal Detail:
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Title: European journal of medical genetics Volume: 52 ISSN: 1878-0849 ISO Abbreviation: Eur J Med Genet Publication Date: 2009 Sep-Oct |
Date Detail:
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Created Date: 2009-08-25 Completed Date: 2009-11-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101247089 Medline TA: Eur J Med Genet Country: Netherlands |
Other Details:
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Languages: eng Pagination: 321-7 Citation Subset: IM |
Affiliation:
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Laboratoire de Cytogénétique, Institut de Puériculture, Paris, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Alleles Chromosome Deletion* Chromosomes, Human, Pair 22* DiGeorge Syndrome / genetics* Gene Frequency Humans In Situ Hybridization, Fluorescence Infant, Newborn Male Physical Chromosome Mapping Polymorphism, Single Nucleotide* T-Box Domain Proteins / genetics* |
| Chemical | |
Reg. No./Substance:
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0/T-Box Domain Proteins; 0/TBX1 protein, human |
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