scholarly journals Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia

2018 ◽  
Vol 27 (7) ◽  
pp. 1196-1211 ◽  
Author(s):  
Patrick Lorès ◽  
Charles Coutton ◽  
Elma El Khouri ◽  
Laurence Stouvenel ◽  
Maëlle Givelet ◽  
...  
Keyword(s):  
Male Infertility ◽  
Missense Mutation ◽  
Adenylate Kinase ◽  
Primary Ciliary Dyskinesia ◽  
Homozygous Missense Mutation ◽  
Morphological Anomalies ◽  
Primary Male ◽  
Ciliary Dyskinesia

Bi-allelic BRWD1 variants cause male infertility with asthenoteratozoospermia and likely primary ciliary dyskinesia

2021 ◽  
Author(s):  
Ting Guo ◽  
Chao-Feng Tu ◽  
Dan-Hui Yang ◽  
Shui-Zi Ding ◽  
Cheng Lei ◽  
...  
Keyword(s):  
Male Infertility ◽  
Primary Ciliary Dyskinesia ◽  
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 Mutations in DNAJB13 , Encoding an HSP40 Family Member, Cause Primary Ciliary Dyskinesia and Male Infertility

2016 ◽  
Vol 99 (2) ◽  
pp. 489-500 ◽  
Author(s):  
Elma El Khouri ◽  
Lucie Thomas ◽  
Ludovic Jeanson ◽  
Emilie Bequignon ◽  
Benoit Vallette ◽  
...  
Keyword(s):  
Male Infertility ◽  
Family Member ◽  
Primary Ciliary Dyskinesia ◽  
Ciliary Dyskinesia

scholarly journals Primary Ciliary Dyskinesia in Mice Lacking the Novel Ciliary Protein Pcdp1

2007 ◽  
Vol 28 (3) ◽  
pp. 949-957 ◽  
Author(s):  
Lance Lee ◽  
Dean R. Campagna ◽  
Jack L. Pinkus ◽  
Howard Mulhern ◽  
Todd A. Wyatt ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Male Infertility ◽  
Primary Ciliary Dyskinesia ◽  
Single Gene ◽  
Ependymal Cells ◽  
The Novel ◽  
Gene Encoding ◽  
Respiratory Epithelial ◽  
Ciliated Epithelial Cells ◽  
Ciliary Dyskinesia

ABSTRACT Primary ciliary dyskinesia (PCD) results from ciliary dysfunction and is commonly characterized by sinusitis, male infertility, hydrocephalus, and situs inversus. Mice homozygous for the nm1054 mutation develop phenotypes associated with PCD. On certain genetic backgrounds, homozygous mutants die perinatally from severe hydrocephalus, while mice on other backgrounds have an accumulation of mucus in the sinus cavity and male infertility. Mutant sperm lack mature flagella, while respiratory epithelial cilia are present but beat at a slower frequency than wild-type cilia. Transgenic rescue demonstrates that the PCD in nm1054 mutants results from the loss of a single gene encoding the novel primary ciliary dyskinesia protein 1 (Pcdp1). The Pcdp1 gene is expressed in spermatogenic cells and motile ciliated epithelial cells. Immunohistochemistry shows that Pcdp1 protein localizes to sperm flagella and the cilia of respiratory epithelial cells and brain ependymal cells in both mice and humans. This study demonstrates that Pcdp1 plays an important role in ciliary and flagellar biogenesis and motility, making the nm1054 mutant a useful model for studying the molecular genetics and pathogenesis of PCD.

Role of Adenylate Kinase Type 7 Expression on Cilia Motility: Possible Link in Primary Ciliary Dyskinesia

2010 ◽  
Vol 24 (3) ◽  
pp. 181-185 ◽  
Author(s):  
Javier Milara ◽  
Miguel Armengot ◽  
Manuel Mata ◽  
Esteban J. Morcillo ◽  
Julio Cortijo
Keyword(s):  
Adenylate Kinase ◽  
Primary Ciliary Dyskinesia ◽  
Ciliary Dyskinesia

219. Parkin co-regulated gene (Pacrg) is an axonemal protein involved in sperm tail and ependymal cell function and is a candidate primary ciliary dyskinesia gene

2008 ◽  
Vol 20 (9) ◽  
pp. 19
Author(s):  
G. R. Wilson ◽  
H. X. Wang ◽  
G. F. Egan ◽  
M. B. Delatycki ◽  
M. K. O.'Bryan ◽  
...  
Keyword(s):  
Male Infertility ◽  
Primary Ciliary Dyskinesia ◽  
Cell Function ◽  
Transgenic Expression ◽  
Microtubule Stability ◽  
Human Male ◽  
Coregulated Gene ◽  
Sperm Counts ◽  
Necessary And Sufficient ◽  
Ciliary Dyskinesia

A leading cause of male infertility is genetic variation in genes required for sperm formation or function. Considerable evidence suggests PACRG is involved in spermiogeneis. The loss of Pacrg function causes infertility in mice (Lorenzetti et al. 2004) and we have shown an association between variability in the 5′ untranslated region of PACRG and human male infertility (Wilson et al. in preparation). Evidence from studies in C.reinhardtii and T.brucei indicate Pacrg is crucial for axonome formation and microtubule stability. To assess this possibility in mammals, we generated and characterised Pacrg knockout (Quaking viable, Qkv), wildtype and Pacrg transgenic mice (Qkv-Tg). Using confocal and immunoelectron microscopy we showed that Pacrg was localised to the axonemal microtubule doublets of sperm, tracheal and ependymal cilia. The absence of Pacrg was associated with compromised sperm flagella formation and MRI analyses revealed the occurrence of hydrocephalus. Specifically, Qkv mice showed an inward expansion of the lateral ventricles, resulting in a significant reduction in distance between ventricles (1.0 ± 0.6 mm, mean ± s.d., n = 5) and a ~250% increase in ventricle area (70 ± 13 arbitrary units, mean ± s.d., n = 5) compared with wildtype littermates (1.38 ± 0.09 mm; area 26 ± 12, n = 3). Transgenic expression of Pacrg was necessary and sufficient to correct the hydrocephalus (1.45 ± 0.05 mm; area 26 ± 9, n = 2) and infertility phenotypes (evidenced by daily sperm counts and litter sizes). In conclusion, we have shown Pacrg is a novel axoneme associated protein in a subset of motile cilia/flagella and loss of Pacrg function results in spermiogenic defects and hydrocephalus in mice. Further, we have shown that variations in the human PACRG promoter are a risk factor in human male infertility. Collectively these data suggest PACRG is a candidate gene in the human syndrome of primary ciliary dyskinesia. (1) Lorenzetti D, Bishop CE, Justice MJ. 2004. Deletion of the Parkin coregulated gene causes male sterility in the quaking (viable) mouse mutant. Proc Natl Acad Sci U S A 101(22):8402–8407

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