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Deletions and point mutations of LRRC50 cause primary ciliary dyskinesia due to dynein arm defects.

Abstract：

:Genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, randomization of left-right body asymmetry, and, frequently, male infertility in primary ciliary dyskinesia (PCD). The most frequent defects involve outer and inner dynein arms (ODAs and IDAs) that are large multiprotein complexes responsible for cilia-beat generation and regulation, respectively. Here, we demonstrate that large genomic deletions, as well as point mutations involving LRRC50, are responsible for a distinct PCD variant that is characterized by a combined defect involving assembly of the ODAs and IDAs. Functional analyses showed that LRRC50 deficiency disrupts assembly of distally and proximally DNAH5- and DNAI2-containing ODA complexes, as well as DNALI1-containing IDA complexes, resulting in immotile cilia. On the basis of these findings, we assume that LRRC50 plays a role in assembly of distinct dynein-arm complexes.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

Loges NT,Olbrich H,Becker-Heck A,Häffner K,Heer A,Reinhard C,Schmidts M,Kispert A,Zariwala MA,Leigh MW,Knowles MR,Zentgraf H,Seithe H,Nürnberg G,Nürnberg P,Reinhardt R,Omran H

doi

10.1016/j.ajhg.2009.10.018

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

883-9

issue

6

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(09)00473-X

journal_volume

85

pub_type

杂志文章

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