Back to Search
Start Over
Mutations in C11orf70 Cause Primary Ciliary Dyskinesia with Randomization of Left/Right Body Asymmetry Due to Defects of Outer and Inner Dynein Arms
- Source :
- American Journal of Human Genetics, 102, 973-984, The American Journal of Human Genetics, American Journal of Human Genetics, 102, 5, pp. 973-984
- Publication Year :
- 2018
-
Abstract
- 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), 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 preassembly factor involved in the pathogenesis of PCD. The identification of additional genetic defects that cause PCD and male infertility is of great importance for the clinic as well as for genetic counselling.
- Subjects :
- Male
0301 basic medicine
primary ciliary dyskinesia
Genes, Recessive
Flagellum
Biology
Male infertility
Pathogenesis
03 medical and health sciences
All institutes and research themes of the Radboud University Medical Center
dynein arm
Genetic
Loss of Function Mutation
Report
Ciliogenesis
preassembly
Genetics
medicine
Humans
Genetics (clinical)
Nuclear Protein
Body Patterning
Primary ciliary dyskinesia
Kartagener Syndrome
Cilium
cilia
Dynein
Dyneins
Nuclear Proteins
C11ORF70
medicine.disease
Sperm
sperm flagella
3. Good health
Cell biology
Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]
030104 developmental biology
Sperm Tail
Mutation
Motile cilium
Female
Human
Subjects
Details
- ISSN :
- 00029297
- Database :
- OpenAIRE
- Journal :
- American Journal of Human Genetics, 102, 973-984, The American Journal of Human Genetics, American Journal of Human Genetics, 102, 5, pp. 973-984
- Accession number :
- edsair.doi.dedup.....24fe4619ded7116fdb4a67544b4ea370