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	Mutations in dnajb13, encoding an hsp40 family member, cause primary ciliary dyskinesia and male infertility
	El Khouri, Elma1,2,3; Thomas, Lucie4; Jeanson, Ludovic4; Bequignon, Emilie5,6,7; Vallette, Benoit4; Duquesnoy, Philippe4; Montantin, Guy8; Copin, Bruno4,8; Moal, Florence Dastot-Le4,8; Blanchon, Sylvain4,9
刊名	American journal of human genetics
	2016-08-04
卷号	99期号:2页码:489-500
ISSN号	0002-9297
DOI	10.1016/j.ajhg.2016.06.022
通讯作者	Toure, aminata(aminata.toure@inserm.fr)
英文摘要	Primary ciliary dyskinesia (pcd) is an autosomal-recessive disease due to functional or ultra-structural defects of motile cilia. affected individuals display recurrent respiratory-tract infections; most males are infertile as a result of sperm flagellar dysfunction. the great majority of the pcd-associated genes identified so far encode either components of dynein arms (das), which are multiprotein-atpase complexes essential for ciliary motility, or proteins involved in da assembly. to identify the molecular basis of a pcd phenotype characterized by central complex (cc) defects but normal da structure, a phenotype found in similar to 15% of cases, we performed whole-exome sequencing in a male individual with pcd and unexplained cc defects. this analysis, combined with whole-genome snp genotyping, identified a homozygous mutation in dnajb13 (c.833t>g), a gene encoding a hsp40 co-chaperone whose ortholog in the flagellated alga chlamydomonas localizes to the radial spokes. in vitro studies showed that this missense substitution (p.met278arg), which involves a highly conserved residue of several hsp40 family members, leads to protein instability and triggers proteasomal degradation, a result confirmed by the absence of endogenous dnajb13 in cilia and sperm from this individual. subsequent dnajb13 analyses identified another homozygous mutation in a second family; the study of dnajb13 transcripts obtained from airway cells showed that this mutation (c.68+1g>c) results in a splicing defect consistent with a loss-of-function mutation. overall, this study, which establishes mutations in dnajb13 as a cause of pcd, unveils the key role played by dnajb13 in the proper formation and function of ciliary and flagellar axonemes in humans.
WOS关键词	RADIAL-SPOKE ; CENTRAL-COMPLEX ; MOLECULAR-CLONING ; PROTEIN ; CHAPERONE ; AXONEME ; BINDING ; HEAT-SHOCK-PROTEIN-40 ; SPERMATOZOA ; FLAGELLUM
WOS研究方向	Genetics & Heredity
WOS类目	Genetics & Heredity
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000381617200021
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2374387
专题	中国科学院大学
通讯作者	Toure, Aminata
作者单位	1.Inst Cochin, INSERM, U1016, F-75014 Paris, France 2.CNRS, UMR8104, F-75014 Paris, France 3.Univ Paris 05, Sorbonne Paris Cite, Fac Med, F-75014 Paris, France 4.Univ Paris 06, INSERM, UMR S933, F-75012 Paris, France 5.Univ Paris Est, CNRS, Fac Med, Equipe 13,INSERM,UMR S955,ERL7240, F-94000 Creteil, France 6.Ctr Hosp Intercommunal Creteil, Serv ORL & Chirurg Cervicofaciale, F-94000 Creteil, France 7.Grp Hosp Henri Mondor Albert Chenevier, Assistance Publ Hop Paris, F-94000 Creteil, France 8.Hop Armand Trousseau, Assistance Publ Hop Paris, Serv Genet & Embryol Med, F-75012 Paris, France 9.Ctr Hosp Univ, Hop Enfants, Unite Pneumol & Allergol Pediat, F-31300 Toulouse, France 10.Hop Bicetre, Assistance Publ Hop Paris, Serv Otorhinolaryngol & Chirurg Cervicomaxillofac, F-94275 Le Kremlin Bicetre, France
推荐引用方式 GB/T 7714	El Khouri, Elma,Thomas, Lucie,Jeanson, Ludovic,et al. Mutations in dnajb13, encoding an hsp40 family member, cause primary ciliary dyskinesia and male infertility[J]. American journal of human genetics,2016,99(2):489-500.
APA	El Khouri, Elma.,Thomas, Lucie.,Jeanson, Ludovic.,Bequignon, Emilie.,Vallette, Benoit.,...&Amselem, Serge.(2016).Mutations in dnajb13, encoding an hsp40 family member, cause primary ciliary dyskinesia and male infertility.American journal of human genetics,99(2),489-500.
MLA	El Khouri, Elma,et al."Mutations in dnajb13, encoding an hsp40 family member, cause primary ciliary dyskinesia and male infertility".American journal of human genetics 99.2(2016):489-500.

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