دورية أكاديمية
IFT81, encoding an IFT-B core protein, as a very rare cause of a ciliopathy phenotype
| العنوان: | IFT81, encoding an IFT-B core protein, as a very rare cause of a ciliopathy phenotype |
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| المساهمون: | College of Medicine, Dept. of Pharmacology, Isabelle Perrault, Jan Halbritter, Jonathan D Porath, Xavier G챕rard, Daniela A Braun, Heon Yung Gee, Hanan M Fathy, Sophie Saunier, Val챕rie Cormier-Daire, Sophie Thomas, Tania Atti챕-Bitach, Nathalie Boddaert, Michael Taschner, Markus Schueler, Esben Lorentzen, Richard P Lifton, Jennifer A Lawson, Meriem Garfa-Traore, Edgar A Otto, Philippe Bastin, Catherine Caillaud, Josseline Kaplan, Jean-Michel Rozet, Friedhelm Hildebrandt, Gee, Heon Yung |
| بيانات النشر: | British Medical Association |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Cilia/genetics, Cilia/pathology, Eye/pathology, Humans, Kidney/pathology, Muscle Proteins/genetics, Mutation, Sequence Analysis, DNA, Genetics, Molecular genetics, Ophthalmology, Renal Medicine |
| الوصف: | BACKGROUND: Bidirectional intraflagellar transport (IFT) consists of two major protein complexes, IFT-A and IFT-B. In contrast to the IFT-B complex, all components of IFT-A have recently been linked to human ciliopathies when defective. We therefore hypothesised that mutations in additional IFT-B encoding genes can be found in patients with multisystemic ciliopathies. METHODS: We screened 1628 individuals with reno-ocular ciliopathies by targeted next-generation sequencing of ciliary candidate genes, including all IFT-B encoding genes. RESULTS: Consequently, we identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. Further, we detected a loss-of-stop mutation with extension of the deduced protein by 10 amino acids in an individual with neuronal ceroid lipofuscinosis-1. This proband presented with retinal dystrophy and brain lesions including cerebellar atrophy, a phenotype to which the IFT81 variant might contribute. Cultured fibroblasts of this latter affected individual showed a significant decrease in ciliated cell abundance compared with controls and increased expression of the transcription factor GLI2 suggesting deranged sonic hedgehog signalling. CONCLUSIONS: This work describes identification of mutations of IFT81 in individuals with symptoms consistent with the clinical spectrum of ciliopathies. It might represent the rare case of a core IFT-B complex protein found associated with human disease. Our data further suggest that defects in the IFT-B core are an exceedingly rare finding, probably due to its indispensable role for ciliary assembly in development. ; open |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0022-2593 1468-6244 |
| العلاقة: | JOURNAL OF MEDICAL GENETICS; J01582; OAK-2015-05416; https://ir.ymlib.yonsei.ac.kr/handle/22282913/156715Test; T201504430; JOURNAL OF MEDICAL GENETICS, Vol.52(10) : 657-665, 2015 |
| DOI: | 10.1136/jmedgenet-2014-102838 |
| الإتاحة: | https://doi.org/10.1136/jmedgenet-2014-102838Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/156715Test |
| حقوق: | CC BY-NC-ND 2.0 KR ; https://creativecommons.org/licenses/by-nc-nd/2.0/krTest/ |
| رقم الانضمام: | edsbas.79202ECF |
| قاعدة البيانات: | BASE |
| تدمد: | 00222593 14686244 |
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| DOI: | 10.1136/jmedgenet-2014-102838 |