Contributors: Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory (LR11IPT05); Université de Tunis El Manar (UTM)-Institut Pasteur de Tunis; Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP); Université Joseph Fourier - Grenoble 1 (UJF); AGeing and IMagery (AGIM); Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École Pratique des Hautes Études (EPHE); Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Centre National de la Recherche Scientifique (CNRS); Laboratoire de Génétique Chromosomique CHU de Grenoble; Centre Hospitalier Universitaire CHU Grenoble (CHUGA); Clinique de Promotion des Sciences de la Reproduction Tunis (CPSR); Polyclinique les Jasmins Tunis; Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM); Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG); Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS); GIN Grenoble Institut des Neurosciences (GIN); Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM); Institut de Biologie et de Pathologie (DBTP); Laboratoire d’Aide à la Procréation, Département de Génétique et Procréation (CECOS); Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-Hôpital Couple Enfant de Grenoble; Physiopathologie des maladies génétiques d'expression pédiatrique; Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM); Institut Cochin (IC UM3 (UMR 8104 / U1016)); Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Dynamiques Cellulaire, Tissulaire & Microscopie fonctionnelle (TIMC-IMAG-DyCTiM); This work was supported by the research grant ICG2I funded by the program GENOPAT 2009 from the French Research Agency (ANR).; ANR-09-GENO-0013,ICG2I,Identification et Caractérisation de gènes impliqués dans l'infertilité.(2009)
نبذة مختصرة : International audience ; Ten to fifteen percent of couples are confronted with infertility and a male factor is involved in approximately half the cases. A genetic etiology is likely in most cases yet only few genes have been formally correlated with male infertility. Homozygosity mapping was carried out on a cohort of 20 North African individuals, including 18 index cases, presenting with primary infertility resulting from impaired sperm motility caused by a mosaic of multiple morphological abnormalities of the flagella (MMAF) including absent, short, coiled, bent, and irregular flagella. Five unrelated subjects out of 18 (28%) carried a homozygous variant in DNAH1, which encodes an inner dynein heavy chain and is expressed in testis. RT-PCR, immunostaining, and electronic microscopy were carried out on samples from one of the subjects with a mutation located on a donor splice site. Neither the transcript nor the protein was observed in this individual, confirming the pathogenicity of this variant. A general axonemal disorganization including mislocalization of the microtubule doublets and loss of the inner dynein arms was observed. Although DNAH1 is also expressed in other ciliated cells, infertility was the only symptom of primary ciliary dyskinesia observed in affected subjects, suggesting that DNAH1 function in cilium is not as critical as in sperm flagellum.
Processing Request
No Comments.