Evaluation of TUBB8 gene alterations in infertile women with oocyte maturation and cleavage arrest referred to Royan Institute

Parnaz Borjian Boroujeni; Kathleen Rooney; Mehdi Alikhani; Saman Rahmati; Ghazaleh Feli; Kaveh Haratian; Bahar Movaghar; Anahita Mohseni Meybodi

doi:10.1016/j.rbmo.2023.04.017

Evaluation of TUBB8 gene alterations in infertile women with oocyte maturation and cleavage arrest referred to Royan Institute

Reprod Biomed Online. 2023 Oct;47(4):103226. doi: 10.1016/j.rbmo.2023.04.017. Epub 2023 May 3.

Authors

Parnaz Borjian Boroujeni¹, Kathleen Rooney², Mehdi Alikhani³, Saman Rahmati⁴, Ghazaleh Feli¹, Kaveh Haratian⁵, Bahar Movaghar⁶, Anahita Mohseni Meybodi⁷

Affiliations

¹ Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
² Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
³ Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
⁴ Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
⁵ Department of Microbiology and Immunology, Medical School, Alborz University of Medical Sciences, Karaj, Iran.
⁶ Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. Electronic address: bhrmovaghar@yahoo.com.
⁷ Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran; Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada. Electronic address: anahita.mohsenimeybodi@lhsc.on.ca.

PMID: 37597348
DOI: 10.1016/j.rbmo.2023.04.017

Abstract

Research question: Are TUBB8 gene variations present in Iranian infertile women with oocyte maturation arrest or embryo cleavage arrest?

Design: TUBB8 gene variations were investigated by polymerase chain reaction sequencing on blood samples from 16 women with oocyte maturation arrest and 12 women with cleavage arrest, collectively referred to as the experimental cohort, as well as 56 fertile women as the control group. The Exome Sequencing Project and dbSNP databases and the Genome Aggregation Database were used to search the frequency of corresponding variants. PolyPhen and SIFT were used to conduct in-silico analysis of gene variations and Align-GVGD was used to predict the effect of missense variants on proteins. The homology modelling and structure evaluation of variations was also checked.

Results: Two likely pathogenic variants [c.713C>T (p.Thr238Met), c.1054G>T (p.Ala352Ser)] were identified in patients with oocyte maturation arrest and one likely pathogenic variant [c.G763A, (p.Val255Met)] was identified in a patient with cleavage arrest. These changes were absent in controls.

Conclusions: Three deleterious variants in TUBB8 related to oocyte maturation arrest or cleavage arrest and infertility were identified. TUBB8 variant screening for patients with oocyte maturation and cleavage arrest is recommended.

Keywords: TUBB8; embryo cleavage arrest; infertility; missense mutation; oocyte maturation arrest; single nucleotide polymorphism.

MeSH terms

Cleavage Stage, Ovum
Female
Fertility
Humans
Infertility, Female* / genetics
Iran
Oocytes
Tubulin / genetics

Substances

TUBB8 protein, human
Tubulin