• PMID: 24360805
• Gene Name: DNAH1
• Condition: Primary infertility, impaired sperm motility
• Association: Associated
• Population size: 20
• Population details: 20 (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)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Primary infertility, impaired sperm motility

Mutations in DNAH1, which encodes an inner arm heavy chain dynein, lead to male infertility from multiple morphological abnormalities of the sperm flagella

Ben Khelifa M, Coutton C, Zouari R, Karaouzène T, Rendu J, Bidart M, Yassine S, Pierre V, Delaroche J, Hennebicq S, Grunwald D, Escalier D, Pernet-Gallay K, Jouk PS, Thierry-Mieg N, Touré A, Arnoult C, Ray PF.

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. CI - Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. FAU - Ben Khelifa, Mariem AU - Ben Khelifa M AD - Université Joseph Fourier, Grenoble 38000, France; Laboratoire AGIM, CNRS FRE3405, Equipe "Andrologie et Génétique," La Tronche 38700, France; Laboratoire de génomique Biomédicale et Oncogénétique, Institut Pasteur de Tunis, 1002 Tunis, Tunisie. FAU - Coutton, Charles AU - Coutton C AD - Université Joseph Fourier, Grenoble 38000, France; Laboratoire AGIM, CNRS FRE3405, Equipe "Andrologie et Génétique," La Tronche 38700, France; CHU de Grenoble, Hôpital Couple Enfant, Département de Génétique et Procréation, Laboratoire de Génétique Chromosomique, Grenoble 38000, France. FAU - Zouari, Raoudha AU - Zouari R AD - Clinique des Jasmins, 23, Av. Louis BRAILLE, 1002 Tunis, Tunisia. FAU - Karaouzène, Thomas AU - Karaouzène T AD - Université Joseph Fourier, Grenoble 38000, France; Laboratoire AGIM, CNRS FRE3405, Equipe "Andrologie et Génétique," La Tronche 38700, France. FAU - Rendu, John AU - Rendu J AD - Université Joseph Fourier, Grenoble 38000, France; CHU de Grenoble, Institut de Biologie et Pathologie, Département de Biochimie, Toxicologie et Pharmacologie (DBTP), UF de Biochimie et Génétique Moléculaire, Grenoble 38000, France; INSERM, U836, Grenoble Institute of Neuroscience, La Tronche 38700, France. FAU - Bidart, Marie AU - Bidart M AD - Université Joseph Fourier, Grenoble 38000, France; INSERM, U836, Grenoble Institute of Neuroscience, La Tronche 38700, France. FAU - Yassine, Sandra AU - Yassine S AD - Université Joseph Fourier, Grenoble 38000, France; Laboratoire AGIM, CNRS FRE3405, Equipe "Andrologie et Génétique," La Tronche 38700, France. FAU - Pierre, Virginie AU - Pierre V AD - Université Joseph Fourier, Grenoble 38000, France; Laboratoire AGIM, CNRS FRE3405, Equipe "Andrologie et Génétique," La Tronche 38700, France. FAU - Delaroche, Julie AU - Delaroche J AD - Université Joseph Fourier, Grenoble 38000, France; INSERM, U836, Grenoble Institute of Neuroscience, La Tronche 38700, France. FAU - Hennebicq, Sylviane AU - Hennebicq S AD - Université Joseph Fourier, Grenoble 38000, France; Laboratoire AGIM, CNRS FRE3405, Equipe "Andrologie et Génétique," La Tronche 38700, France; CHU de Grenoble, Hôpital Couple Enfant, Département de Génétique et Procréation, Laboratoire d'Aide à la Procréation - CECOS, Grenoble 38000, France. FAU - Grunwald, Didier AU - Grunwald D AD - Université Joseph Fourier, Grenoble 38000, France; INSERM, U836, Grenoble Institute of Neuroscience, La Tronche 38700, France. FAU - Escalier, Denise AU - Escalier D AD - INSERM UMR_S933, Université Pierre et Marie Curie (Paris 6), Paris 75012, France. FAU - Pernet-Gallay, Karine AU - Pernet-Gallay K AD - Université Joseph Fourier, Grenoble 38000, France; INSERM, U836, Grenoble Institute of Neuroscience, La Tronche 38700, France. FAU - Jouk, Pierre-Simon AU - Jouk PS AD - Université Joseph Fourier-Grenoble 1 / CNRS / TIMC-IMAG UMR 5525, Grenoble 38041, France; CHU de Grenoble, Hôpital Couple Enfant, Département de Génétique et Procréation, Service de Génétique Clinique, Grenoble 38000, France. FAU - Thierry-Mieg, Nicolas AU - Thierry-Mieg N AD - Université Joseph Fourier-Grenoble 1 / CNRS / TIMC-IMAG UMR 5525, Grenoble 38041, France. FAU - Touré, Aminata AU - Touré A AD - INSERM, U1016, Institut Cochin, Paris 75014, France; CNRS, UMR8104, Paris 75014, France; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris 75014, France. FAU - Arnoult, Christophe AU - Arnoult C AD - Université Joseph Fourier, Grenoble 38000, France; Laboratoire AGIM, CNRS FRE3405, Equipe "Andrologie et Génétique," La Tronche 38700, France.