Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Outer Dynein Arm Heavy Chain, Cause Isolated Male Infertility Due to Asthenozoospermia

Motile cilia and sperm flagella share an evolutionarily conserved axonemal structure. Their structural and/or functional defects are associated with primary ciliary dyskinesia (PCD), a genetic disease characterized by chronic respiratory-tract infections and in which most males are infertile due to asthenozoospermia. Among the well-characterized axonemal protein complexes, the outer dynein arms (ODAs), through ATPase activity of their heavy chains (HCs), play a major role for cilia and flagella beating.
Source: The American Journal of Human Genetics - Category: Genetics & Stem Cells Authors: Tags: Report Source Type: research

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Primary ciliary dyskinesia (PCD) is a genetically and clinically heterogeneous disease, usually inherited in an autosomal recessive pattern. Patients with PCD develop recurrent and chronic infections of upper and lower airways, invariably leading to bronchiectasis and impaired lung function. Conductive hearing impairment is common and half of people with PCD have situs abnormalities, e.g. situs inversus or situs ambiguus, which can be associated with congenital heart disease. Many, but not all men are infertile due to immotile sperm, and some women are sub-fertile because of immotile cilia in the Fallopian tubes [1].
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Editorials Source Type: research
This article has an associated First Person interview with the joint first authors of the paper.
Source: DMM Disease Models and Mechanisms - Category: Biomedical Science Authors: Tags: RESEARCH ARTICLE Source Type: research
Abstract The syndrome of multiple morphological abnormalities of the sperm flagella (MMAF) is a specific kind of asthenoteratozoospermia with a mosaic of flagellar morphological abnormalities (absent, short, bent, coiled, and irregular flagella). MMAF was proposed in 2014 and has attracted increasing attention; however, it has not been clearly understood. In this review, we elucidate the definition of MMAF from a systematical view, the difference between MMAF and other conditions with asthenoteratozoospermia or asthenozoospermia (such as primary mitochondrial sheath defects and primary ciliary dyskinesia), the kno...
Source: Asian Journal of Andrology - Category: Urology & Nephrology Authors: Tags: Asian J Androl Source Type: research
Abstract Reduced or no progressive sperm motility in the fresh ejaculate defines asthenozoospermia as one of the major causes of male infertility. The axonemal heavy chain dynein type 11 ( DNAH11 ) gene encodes for one of the axonemal dynein heavy chain (DHC) family members and participates in assembling respiratory cilia and sperm flagella. Given the high degree of conservation of DNAH11 , mutations could give rise to primary ciliary dyskinesia (PCD) and asthenozoospermia. To date, few studies have reported on the association between variants in DNAH11 and asthenozoospermia. In the present study, 87 patients with...
Source: Bioscience Reports - Category: Biomedical Science Authors: Tags: Biosci Rep Source Type: research
AbstractMale infertility due to Multiple Morphological Abnormalities of the sperm Flagella (MMAF), is characterized by nearly total asthenozoospermia due to the presence of a mosaic of sperm flagellar anomalies, which corresponds to short, angulated, absent flagella and flagella of irregular calibre. In the last four years, 7 novel genes whose mutations account for 45% of a cohort of 78 MMAF individuals were identified:DNAH1,CFAP43,CFAP44,CFAP69,FSIP2,WDR66 (CFAP251), AK7. This successful outcome results from the efficient combination of high-throughput sequencing technologies together with robust and complementary approac...
Source: Basic and Clinical Andrology - Category: Urology & Nephrology Source Type: research
In this report, we summarize the meeting, highlighting developments made during the meeting.
Source: BMC Proceedings - Category: Biomedical Science Source Type: research
Flagella and motile cilia share a 9  + 2 microtubule-doublet axoneme structure, and asthenozoospermia (reduced spermatozoa motility) is found in 76% of men with primary ciliary dyskinesia (PCD). Nevertheless, causal genetic variants in a conserved axonemal component have been found in cases of isolated asthenozoospermia: 30% of men w ith multiple morphological anomalies of sperm flagella (MMAF) carry bi-allelic mutations in DNAH1, encoding one of the seven inner-arm dynein heavy chains of the 9 + 2 axoneme.
Source: The American Journal of Human Genetics - Category: Genetics & Stem Cells Authors: Tags: Report Source Type: research
We describe the main PCD diagnostic tests and compare the two international PCD diagnostic guidelines. The expensive multi-test diagnostic approach requiring a high level of expertise and specialist equipment, make the multifaceted PCD diagnostic pathway complex. Therefore, the risk of late or missed diagnosis is high and has clinical and research implications.Defining the number of patients with bronchiectasis due to PCD is complex. To date, few studies outlining the aetiology of adult patients with bronchiectasis conduct screening tests for PCD, but they do differ in their diagnostic approach. Comparison of these studies...
Source: Multidisciplinary Respiratory Medicine - Category: Respiratory Medicine Source Type: research
Abstract Primary ciliary dyskinesia is a rare genetic disease of the motile cilia, one of a rapidly expanding collection of disorders known as ciliopathies. Patients with primary ciliary dyskinesia have diverse clinical manifestations, including chronic upper and lower respiratory tract disease, left-right laterality defects, and infertility. In recent years, our understanding of the genetics of primary ciliary dyskinesia has rapidly advanced. A growing number of disease-associated genes and pathogenic mutations have been identified, which encode axonemal, cytoplasmic, and regulatory proteins involved in the assem...
Source: Chest - Category: Respiratory Medicine Authors: Tags: Chest Source Type: research
Primary ciliary dyskinesia (PCD) is characterized by chronic airway disease, male infertility, and randomization of the left/right body axis as a result of 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, as a result of the loss of axonemal outer (ODAs) and inner dynein arms (IDAs), indicat...
Source: The American Journal of Human Genetics - Category: Genetics & Stem Cells Authors: Tags: Report Source Type: research
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