Homozygous loss-of-function mutations in MNS1 cause laterality defects and likely male infertility

• Published in: PLoS genetics Vol. 14; no. 8; p. e1007602
• Main Authors: Ta-Shma, Asaf, Hjeij, Rim, Perles, Zeev, Dougherty, Gerard W, Abu Zahira, Ibrahim, Letteboer, Stef J F, Antony, Dinu, Darwish, Alaa, Mans, Dorus A, Spittler, Sabrina, Edelbusch, Christine, Cindrić, Sandra, Nöthe-Menchen, Tabea, Olbrich, Heike, Stuhlmann, Friederike, Aprea, Isabella, Pennekamp, Petra, Loges, Niki T, Breuer, Oded, Shaag, Avraham, Rein, Azaria J J T, Gulec, Elif Yilmaz, Gezdirici, Alper, Abitbul, Revital, Elias, Nael, Amirav, Israel, Schmidts, Miriam, Roepman, Ronald, Elpeleg, Orly, Omran, Heymut
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.08.2018; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Animals; Axonemal Dyneins - genetics; Axonemal Dyneins - metabolism; Axoneme - metabolism; Axonemes; Biology and Life Sciences; Cardiology; Child; Child, Preschool; Cilia; Cilia - ultrastructure; Codon, Nonsense; Defects; Dynein; Embryos; Epithelial cells; Exome sequencing; Female; Flagella; Functional Laterality - genetics; Funding; Gene Expression Regulation; Gene mutation; Genetic aspects; Genetic Linkage; Genetic research; Health sciences; Homozygosity; Homozygote; Hospitals; Humans; Hydrocephalus; Immunofluorescence; Immunoprecipitation; Infant; Infertility; Infertility, Male - genetics; Inversion; Life sciences; Linkage analysis; Male; Male infertility; Medicine; Medicine and Health Sciences; Mice; Mice, Knockout; Middle Aged; Mutation; Nonsense mutation; Nuclear Proteins - deficiency; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Pediatrics; Pedigree; Polymorphism, Single Nucleotide; Proteins; Research and Analysis Methods; Respiratory system; Signal transduction; Situs inversus; Sperm Tail; Supervision; Whole Exome Sequencing; Young Adult; Istanbul Turkey; Netherlands; Turkey; Israel; Jerusalem Israel; Tel Aviv Israel; Germany

The clinical spectrum of ciliopathies affecting motile cilia spans impaired mucociliary clearance in the respiratory system, laterality defects including heart malformations, infertility and hydrocephalus. Using linkage analysis and whole exome sequencing, we identified two recessive loss-of-functio...