scholarly journals Loss of function of axonemal dynein Mdnah5 causes primary ciliary dyskinesia and hydrocephalus

2002 ◽  
Vol 11 (6) ◽  
pp. 715-721 ◽  
Author(s):  
I. Ibanez-Tallon
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Loss Of Function ◽  
Axonemal Dynein ◽  
Ciliary Dyskinesia

scholarly journals Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia

2012 ◽  
Vol 44 (4) ◽  
pp. 381-389 ◽  
Author(s):  
Hannah M Mitchison ◽  
Miriam Schmidts ◽  
Niki T Loges ◽  
Judy Freshour ◽  
Athina Dritsoula ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Assembly Factor ◽  
Axonemal Dynein ◽  
Ciliary Dyskinesia

scholarly journals Loss-of-Function Mutations in RSPH1 Cause Primary Ciliary Dyskinesia with Central-Complex and Radial-Spoke Defects

2013 ◽  
Vol 93 (3) ◽  
pp. 561-570 ◽  
Author(s):  
Esther Kott ◽  
Marie Legendre ◽  
Bruno Copin ◽  
Jean-François Papon ◽  
Florence Dastot-Le Moal ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Central Complex ◽  
Loss Of Function ◽  
Radial Spoke ◽  
Ciliary Dyskinesia

scholarly journals Loss-of-Function Mutations in a Human Gene Related to Chlamydomonas reinhardtii Dynein IC78 Result in Primary Ciliary Dyskinesia

1999 ◽  
Vol 65 (6) ◽  
pp. 1508-1519 ◽  
Author(s):  
Gaëlle Pennarun ◽  
Estelle Escudier ◽  
Catherine Chapelin ◽  
Anne-Marie Bridoux ◽  
Valère Cacheux ◽  
...  
Keyword(s):  
Chlamydomonas Reinhardtii ◽  
Primary Ciliary Dyskinesia ◽  
Human Gene ◽  
Loss Of Function ◽  
Ciliary Dyskinesia

scholarly journals Mutations in C11ORF70 cause primary ciliary dyskinesia with randomization of left/right body asymmetry due to outer and inner dynein arm defects

2017 ◽  
Author(s):  
Inga M. Höben ◽  
Rim Hjeij ◽  
Heike Olbrich ◽  
Gerard W. Dougherty ◽  
Tabea Menchen ◽  
...  
Keyword(s):  
Male Infertility ◽  
Primary Ciliary Dyskinesia ◽  
Genetic Defect ◽  
Clinical Importance ◽  
Airway Disease ◽  
Cytoplasmic Dynein ◽  
Loss Of Function ◽  
Reading Frame ◽  
Dynein Arms ◽  
Ciliary Dyskinesia

AbstractPrimary ciliary dyskinesia (PCD) is characterized by chronic airway disease, male infertility and randomization of the left/right body axis caused by defects of motile cilia and sperm flagella. We identified loss-of-function mutations in the open reading frame C11ORF70 in PCD individuals from five distinct families. Transmission electron microscopy analyses and high resolution immunofluorescence microscopy demonstrate that loss-of-function mutations in C11ORF70 cause immotility of respiratory cilia and sperm flagella, respectively, due to loss of axonemal outer (ODAs) and inner dynein arms (IDAs), indicating that C11ORF70 is involved in cytoplasmic assembly of dynein arms. Expression analyses of C11ORF70 showed that C11ORF70 is expressed in ciliated respiratory cells and that the expression of C11ORF70 is upregulated during ciliogenesis, similar to other previously described cytoplasmic dynein arm assembly factors. Furthermore, C11ORF70 shows an interaction with cytoplasmic ODA/IDA assembly factor DNAAF2, supporting our hypothesis that C11ORF70 is a novel preassembly factor involved in the pathogenesis of PCD. The identification of a novel genetic defect that causes PCD and male infertility is of great clinical importance as well as for genetic counselling.

scholarly journals The Drosophila orthologue of the primary ciliary dyskinesia-associated gene, DNAAF3, is required for axonemal dynein assembly

2021 ◽  
Author(s):  
Petra zur Lage ◽  
Zhiyan Xi ◽  
Jennifer Lennon ◽  
Iain Hunter ◽  
Wai Kit Chan ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Cell Types ◽  
Drosophila Cell ◽  
Heavy Chains ◽  
Neuron Response ◽  
Dynein Motor ◽  
Assembly Factor ◽  
Axonemal Dynein ◽  
Dynein Arms ◽  
Ciliary Dyskinesia

Ciliary motility is powered by a suite of highly conserved axoneme-specific dynein motor complexes. In humans the impairment of these motors through mutation results in the disease, Primary Ciliary Dyskinesia (PCD). Studies in Drosophila have helped to validate several PCD genes whose products are required for cytoplasmic pre-assembly of axonemal dynein motors. Here we report the characterisation of the Drosophila homologue of the less known assembly factor, DNAAF3. This gene, CG17669 (Dnaaf3), is expressed exclusively in developing mechanosensory chordotonal (Ch) neurons and spermatocytes, the only two Drosophila cell types bearing motile cilia/flagella. Mutation of Dnaaf3 results in larvae that are deaf and adults that are uncoordinated, indicating defective Ch neuron function. The mutant Ch neuron cilia of the antenna specifically lack dynein arms, while Ca imaging in larvae reveals a complete loss of Ch neuron response to vibration stimulus, confirming that mechanotransduction relies on ciliary dynein motors. Mutant males are infertile with immotile sperm whose flagella lack dynein arms and show axoneme disruption. Analysis of proteomic changes suggest a reduction in heavy chains of all axonemal dynein forms, consistent with an impairment of dynein pre-assembly.

scholarly journals TTC12 Loss-of-Function Mutations Cause Primary Ciliary Dyskinesia and Unveil Distinct Dynein Assembly Mechanisms in Motile Cilia Versus Flagella

2020 ◽  
Vol 106 (2) ◽  
pp. 153-169 ◽  
Author(s):  
Lucie Thomas ◽  
Khaled Bouhouche ◽  
Marjorie Whitfield ◽  
Guillaume Thouvenin ◽  
Andre Coste ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Loss Of Function ◽  
Motile Cilia ◽  
Ciliary Dyskinesia

Novel Pathogenic DNAH5 Variants in Primary Ciliary Dyskinesia: Association with Visceral Heterotaxia and Neonatal Cholestasis

2021 ◽  
Author(s):  
Hong T. Lin ◽  
Anita Gupta ◽  
Kevin E. Bove ◽  
Sara Szabo ◽  
Fang Xu ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Autosomal Recessive ◽  
Neonatal Cholestasis ◽  
Uncertain Significance ◽  
A Subunit ◽  
Axonemal Dynein ◽  
Infantile Cholestasis ◽  
First Time ◽  
Ciliary Dyskinesia ◽  
Laterality Defects

AbstractThe dynein axonemal heavy chain 5 gene codes for a subunit of axonemal dynein necessary for ciliary motor function. Though research has elucidated the consequences of some variants in this gene, it is still unclear whether many variants in the DNAH5 locus are benign or pathogenic due to the rarity of primary ciliary dyskinesia (PCD, of which Kartagener's syndrome is a subset). Here, we introduce the case of an infant boy presenting with the classical findings of PCD along with visceral heterotaxia and neonatal cholestasis. Genetic testing indicated that the patient is a compound heterozygote with a pathogenic c.8498G > A (known as pathogenic) on the maternally derived allele and two variants of uncertain significance, c.1206T > A and c.7800T > G, on the paternally derived allele. As PCD is autosomal recessive, we conclude that one, or both, of these paternally derived variants are pathogenic. To our knowledge, this is the first time that the clinical implications of c.1206T > A (p.Asn402Lys) and c.7800T > G (p.Ile2600Met) are documented. Furthermore, we use this case as an example to recommend clinicians to assess for PCD and laterality defects when presented with severe infantile cholestasis. While the association of cholestasis with PCD is relatively uncommon, PCD is a risk factor for increased prevalence of biliary atresia and infections, both of which are known causes of cholestasis in early infancy.

Sign in / Sign up

Export Citation Format

Share Document