| Characterization of the chromosome 1q41q42.12 region, and the candidate gene DISP1, in patients with CDH. | |
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MedLine Citation:
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PMID: 20799323 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cytogenetic and molecular cytogenetic studies demonstrate association between congenital diaphragmatic hernia (CDH) and chromosome 1q41q42 deletions. In this study, we screened a large CDH cohort (N=179) for microdeletions in this interval by the multiplex ligation-dependent probe amplification (MLPA) technique, and also sequenced two candidate genes located therein, dispatched 1 (DISP1) and homo sapiens H2.0-like homeobox (HLX). MLPA analysis verified deletions of this region in two cases, an unreported patient with a 46,XY,del(1)(q41q42.13) karyotype and a previously reported patient with a Fryns syndrome phenotype [Kantarci et al., 2006]. HLX sequencing showed a novel but maternally inherited single nucleotide variant (c.27C>G) in a patient with isolated CDH, while DISP1 sequencing revealed a mosaic de novo heterozygous substitution (c.4412C>G; p.Ala1471Gly) in a male with a left-sided Bochdalek hernia plus multiple other anomalies. Pyrosequencing demonstrated the mutant allele was present in 43%, 12%, and 4.5% of the patient's lymphoblastoid, peripheral blood lymphocytes, and saliva cells, respectively. We examined Disp1 expression at day E11.5 of mouse diaphragm formation and confirmed its presence in the pleuroperitoneal fold, as well as the nearby lung which also expresses Sonic hedgehog (Shh). Our report describes the first de novo DISP1 point mutation in a patient with complex CDH. Combining this finding with Disp1 embryonic mouse diaphragm and lung tissue expression, as well as previously reported human chromosome 1q41q42 aberrations in patients with CDH, suggests that DISP1 may warrant further consideration as a CDH candidate gene. |
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Authors:
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Sibel Kantarci; Kate G Ackerman; Meaghan K Russell; Mauro Longoni; Carrie Sougnez; Kristin M Noonan; Eli Hatchwell; Xiaoyun Zhang; Rafael Pieretti Vanmarcke; Kwame Anyane-Yeboa; Paul Dickman; Jay Wilson; Patricia K Donahoe; Barbara R Pober |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: American journal of medical genetics. Part A Volume: 152A ISSN: 1552-4833 ISO Abbreviation: Am. J. Med. Genet. A Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-27 Completed Date: 2010-11-16 Revised Date: 2012-01-31 |
Medline Journal Info:
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Nlm Unique ID: 101235741 Medline TA: Am J Med Genet A Country: United States |
Other Details:
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Languages: eng Pagination: 2493-504 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Wiley-Liss, Inc. |
Affiliation:
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Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Child Chromosome Mapping Chromosomes, Human, Pair 1* Congenital Abnormalities / genetics* DNA / blood, genetics, isolation & purification DNA Primers Female Hedgehog Proteins / genetics Hernia, Diaphragmatic / genetics* Humans In Situ Hybridization, Fluorescence Infant, Newborn Informed Consent Lung / physiology Male Mosaicism Sequence Deletion |
| Grant Support | |
ID/Acronym/Agency:
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R01 HD055150-03/HD/NICHD NIH HHS; R01 HD055150-04/HD/NICHD NIH HHS; R01 HD55150-01/HD/NICHD NIH HHS; R01 HL085459-03/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/Hedgehog Proteins; 0/SHH protein, human; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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