Journal article
Mutation in CATIP (C2orf62) causes oligoteratoasthenozoospermia by affecting actin dynamics
Journal of medical genetics, Vol.58(2), pp.106-115
02/2021
DOI: 10.1136/jmedgenet-2019-106825
PMID: 32503832
Abstract
BackgroundOligoteratoasthenozoospermia (OTA) combines deteriorated quantity, morphology and motility of the sperm, resulting in male factor infertility.MethodsWe used whole genome genotyping and exome sequencing to identify the mutation causing OTA in four men in a consanguineous Bedouin family. We expressed the normal and mutated proteins tagged with c-Myc at the carboxy termini by transfection with pCDNA3.1 plasmid constructs to evaluate the effects on protein stability in HEK293 cells and on the kinetics of actin repolymerisation in retinal pigment epithelium cells. Patients’ sperm samples were visualised by transmission electron microscopy to determine axoneme structures and were stained with fluorescent phalloidin to visualise the fibrillar (F)-actin.ResultsA homozygous missense mutation in Ciliogenesis Associated TTC17 Interacting Protein (CATIP): c. T103A, p. Phe35Ile, a gene encoding a protein important in actin organisation and ciliogenesis, was identified as the causative mutation with a LOD score of 3.25. The mutation reduces the protein stability compared with the normal protein. Furthermore, overexpression of the normal protein, but not the mutated protein, inhibits repolymerisation of actin after disruption with cytochalasin D. A high percentage of spermatozoa axonemes from patients have abnormalities, as well as disturbances in the distribution of F-actin.ConclusionThis is the first report of a recessive mutation in CATIP in humans. The identified mutation may contribute to asthenozoospermia by its involvement in actin polymerisation and on the actin cytoskeleton. A mouse knockout homozygote for CATIP was reported to demonstrate male infertility as the sole phenotype.
Details
- Title: Subtitle
- Mutation in CATIP (C2orf62) causes oligoteratoasthenozoospermia by affecting actin dynamics
- Creators
- Maram Arafat - The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, IsraelAvi Harlev - Fertility and IVF Unit, Department of Obstetrics and Gynecology, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, IsraelIris Har-Vardi - Fertility and IVF Unit, Department of Obstetrics and Gynecology, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, IsraelEliahu Levitas - The Center of Advanced Research and Education in Reproduction (CARER), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, IsraelTsvia Priel - Fertility and IVF Unit, Department of Obstetrics and Gynecology, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, IsraelMoran Gershoni - ARO- The Volcani Center, Institute of Animal Science, Rehovot - Faculty of Agriculture Bet Dagan, Rishon LeZion, IsraelCharles Searby - Department of Pediatrics and Ophthalmology, Division of Medical Genetics, University of Iowa, Iowa City, Iowa, USAVal C Sheffield - Department of Pediatrics and Ophthalmology, Division of Medical Genetics, University of Iowa, Iowa City, Iowa, USAEitan Lunenfeld - The Center of Advanced Research and Education in Reproduction (CARER), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, IsraelRuti Parvari - The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, Israel
- Resource Type
- Journal article
- Publication Details
- Journal of medical genetics, Vol.58(2), pp.106-115
- DOI
- 10.1136/jmedgenet-2019-106825
- PMID
- 32503832
- NLM abbreviation
- J Med Genet
- ISSN
- 0022-2593
- eISSN
- 1468-6244
- Grant note
- name: Ben-Gurion University of the Negev, Faculty of Health Sciences; name: The Israeli Ministry of Science, Technology and Space
- Language
- English
- Date published
- 02/2021
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984070715402771
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