دورية أكاديمية
أعرض في EDS

TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.

التفاصيل البيبلوغرافية
العنوان: TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.
المؤلفون: Davis EE; Center for Human Disease Modeling, Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA., Zhang Q, Liu Q, Diplas BH, Davey LM, Hartley J, Stoetzel C, Szymanska K, Ramaswami G, Logan CV, Muzny DM, Young AC, Wheeler DA, Cruz P, Morgan M, Lewis LR, Cherukuri P, Maskeri B, Hansen NF, Mullikin JC, Blakesley RW, Bouffard GG, Gyapay G, Rieger S, Tönshoff B, Kern I, Soliman NA, Neuhaus TJ, Swoboda KJ, Kayserili H, Gallagher TE, Lewis RA, Bergmann C, Otto EA, Saunier S, Scambler PJ, Beales PL, Gleeson JG, Maher ER, Attié-Bitach T, Dollfus H, Johnson CA, Green ED, Gibbs RA, Hildebrandt F, Pierce EA, Katsanis N
مؤلفون مشاركون: NISC Comparative Sequencing Program
المصدر: Nature genetics [Nat Genet] 2011 Mar; Vol. 43 (3), pp. 189-96. Date of Electronic Publication: 2011 Jan 23.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Nature Pub. Co., c1992-
مواضيع طبية MeSH: Alleles*, Adaptor Proteins, Signal Transducing/*genetics , Ciliary Motility Disorders/*genetics, Animals ; Genetic Variation ; Humans ; Mice ; Mutation ; Pedigree ; Photoreceptor Cells/physiology ; Zebrafish/genetics
مستخلص: Ciliary dysfunction leads to a broad range of overlapping phenotypes, collectively termed ciliopathies. This grouping is underscored by genetic overlap, where causal genes can also contribute modifier alleles to clinically distinct disorders. Here we show that mutations in TTC21B, which encodes the retrograde intraflagellar transport protein IFT139, cause both isolated nephronophthisis and syndromic Jeune asphyxiating thoracic dystrophy. Moreover, although resequencing of TTC21B in a large, clinically diverse ciliopathy cohort and matched controls showed a similar frequency of rare changes, in vivo and in vitro evaluations showed a significant enrichment of pathogenic alleles in cases (P < 0.003), suggesting that TTC21B contributes pathogenic alleles to ∼5% of ciliopathy cases. Our data illustrate how genetic lesions can be both causally associated with diverse ciliopathies and interact in trans with other disease-causing genes and highlight how saturated resequencing followed by functional analysis of all variants informs the genetic architecture of inherited disorders.
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معلومات مُعتمدة: R01DK064614 United States DK NIDDK NIH HHS; G9901217 United Kingdom MRC_ Medical Research Council; G0700073 United Kingdom MRC_ Medical Research Council; R01 DK072301 United States DK NIDDK NIH HHS; R01DK068306 United States DK NIDDK NIH HHS; United States HHMI Howard Hughes Medical Institute; F32 DK079541-04 United States DK NIDDK NIH HHS; G0601347 United Kingdom MRC_ Medical Research Council; R01DK069274 United States DK NIDDK NIH HHS; R01 DK068306 United States DK NIDDK NIH HHS; F32 DK079541 United States DK NIDDK NIH HHS; R01 NS048453 United States NS NINDS NIH HHS; U54 HG003273 United States HG NHGRI NIH HHS; R01 EY012910 United States EY NEI NIH HHS; R01 NS052455 United States NS NINDS NIH HHS; R01EY12910 United States EY NEI NIH HHS; United States ImNIH Intramural NIH HHS; R01 DK075972 United States DK NIDDK NIH HHS; R01 DK069274 United States DK NIDDK NIH HHS; G0801843 United Kingdom MRC_ Medical Research Council; RG/10/13/28570 United Kingdom BHF_ British Heart Foundation; R01 DK064614 United States DK NIDDK NIH HHS; R01DK075972 United States DK NIDDK NIH HHS; R01HD04260 United States HD NICHD NIH HHS; R01DK072301 United States DK NIDDK NIH HHS
سلسلة جزيئية: RefSeq NM_001128258; NM_024753; NP_079029
المشرفين على المادة: 0 (Adaptor Proteins, Signal Transducing)
0 (Ttc21b protein, mouse)
تواريخ الأحداث: Date Created: 20110125 Date Completed: 20110419 Latest Revision: 20220223
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC3071301
DOI: 10.1038/ng.756
PMID: 21258341
قاعدة البيانات: MEDLINE
الوصف
تدمد:1546-1718
DOI:10.1038/ng.756