174 222

Cited 40 times in

Mutations of CEP83 cause infantile nephronophthisis and intellectual disability

Authors
 Marion Failler  ;  Heon Yung Gee  ;  Pauline Krug  ;  Kwangsic Joo  ;  Jan Halbritter  ;  Lilya Belkacem  ;  Emilie Filhol  ;  Jonathan D. Porath  ;  Daniela A. Braun  ;  Markus Schueler  ;  Amandine Frigo  ;  Olivier Alibeu  ;  Ce´cile Masson  ;  Karine Brochard  ;  Bruno Hurault de Ligny  ;  Robert Novo  ;  Christine Pietrement  ;  Hulya Kayserili  ;  Re´mi Salomon  ;  Marie-Claire Gubler  ;  Edgar A. Otto  ;  Corinne Antignac  ;  Joon Kim  ;  Alexandre Benmerah  ;  Friedhelm Hildebrandt  ;  Sophie Saunier 
Citation
 AMERICAN JOURNAL OF HUMAN GENETICS, Vol.94(6) : 905-914, 2014 
Journal Title
 AMERICAN JOURNAL OF HUMAN GENETICS 
ISSN
 0002-9297 
Issue Date
2014
MeSH
Alleles ; Central Nervous System/abnormalities ; Centrioles/genetics ; Centrioles/metabolism ; Child, Preschool ; Cilia/metabolism ; Exons ; Female ; Humans ; Infant ; Intellectual Disability/genetics* ; Kidney Diseases, Cystic/genetics* ; Male ; Microtubule-Associated Proteins/genetics* ; Microtubule-Associated Proteins/metabolism ; Mutation* ; Orofaciodigital Syndromes/genetics
Abstract
Ciliopathies are a group of hereditary disorders associated with defects in cilia structure and function. The distal appendages (DAPs) of centrioles are involved in the docking and anchoring of the mother centriole to the cellular membrane during ciliogenesis. The molecular composition of DAPs was recently elucidated and mutations in two genes encoding DAPs components (CEP164/NPHP15, SCLT1) have been associated with human ciliopathies, namely nephronophthisis and orofaciodigital syndrome. To identify additional DAP components defective in ciliopathies, we independently performed targeted exon sequencing of 1,221 genes associated with cilia and 5 known DAP protein-encoding genes in 1,255 individuals with a nephronophthisis-related ciliopathy. We thereby detected biallelic mutations in a key component of DAP-encoding gene, CEP83, in seven families. All affected individuals had early-onset nephronophthisis and four out of eight displayed learning disability and/or hydrocephalus. Fibroblasts and tubular renal cells from affected individuals showed an altered DAP composition and ciliary defects. In summary, we have identified mutations in CEP83, another DAP-component-encoding gene, as a cause of infantile nephronophthisis associated with central nervous system abnormalities in half of the individuals.
Files in This Item:
T201406465.pdf Download
DOI
10.1016/j.ajhg.2014.05.002
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/158643
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links