A Case of Oocyte Maturation Arrest Caused by Heterozygous Variation of TUBB8 Gene c.154-156del

doi:10.12280/gjszjk.20230220

Abstract

Abstract:

Whole exome sequencing was carried out in a patient with oocyte maturation arrest, and the suspected pathogenic variants were screened by bioinformatics and verified by Sanger sequencing on the patient and her family members. A heterozygous deletion variant of the TUBB8 gene c.154-156del(p.52del) was identified in the patient, but was not found in her parents, brother, sister and niece. Both her brother and sister gave birth. This variant co-segregated with the phenotype. The c.154-156del(p.52del) heterozygous deletion variant of the TUBB8 gene may be the genetic cause of this patient with oocyte maturation arrest. TUBB8 gene mutation accounts for about 30% of patients with oocyte maturation arrest. For the patients with oocyte maturation arrest, TUBB8 gene test can be routinely performed in genetic counseling. The patients caused by TUBB8 gene mutation can only conceive through oocyte donation.

Key words: Tubulin, Genes, Mutation, Oocytes, Infertility, female, TUBB8 gene

WEN Xing-xing, CHAI Meng-han, YANG Ni, ZOU Hui-juan, ZHANG Zhi-guo, LI Lin, CHEN Bei-li. A Case of Oocyte Maturation Arrest Caused by Heterozygous Variation of TUBB8 Gene c.154-156del[J]. Journal of International Reproductive Health/Family Planning, 2024, 43(1): 17-19.

Figures/Tables 4

References 11

[1]	Feng R, Sang Q, Kuang Y, et al. Mutations in TUBB8 and Human Oocyte Meiotic Arrest[J]. N Engl J Med, 2016, 374(3):223-232. doi: 10.1056/NEJMoa1510791.
[2]	Solovova OA, Chernykh VB. Genetics of Oocyte Maturation Defects and Early Embryo Development Arrest[J]. Genes(Basel), 2022, 13(11):1920. doi: 10.3390/genes13111920.
[3]	Cao T, Guo J, Xu Y, et al. Two mutations in TUBB8 cause developmental arrest in human oocytes and early embryos[J]. Reprod Biomed Online, 2021, 43(5):891-898. doi: 10.1016/j.rbmo.2021.07.020. pmid: 34509376
[4]	Yang P, Yin C, Li M, et al. Mutation analysis of tubulin beta 8 class Ⅷ in infertile females with oocyte or embryonic defects[J]. Clin Genet, 2021, 99(1):208-214. doi: 10.1111/cge.13855.
[5]	Sha Q, Zheng W, Feng X, et al. Novel mutations in TUBB8 expand the mutational and phenotypic spectrum of patients with zygotes containing multiple pronuclei[J]. Gene, 2021, 769:145227. doi: 10.1016/j.gene.2020.145227.
[6]	Liu Z, Xi Q, Zhu L, et al. TUBB8 Mutations Cause Female Infertility with Large Polar Body Oocyte and Fertilization Failure[J]. Reprod Sci, 2021, 28(10):2942-2950. doi: 10.1007/s43032-021-00633-z. pmid: 34160777
[7]	Jia Y, Li K, Zheng C, et al. Identification and rescue of a novel TUBB8 mutation that causes the first mitotic division defects and infertility[J]. J Assist Reprod Genet, 2020, 37(11):2713-2722. doi: 10.1007/s10815-020-01945-w.
[8]	Lu Q, Zhang X, Cao Q, et al. Expanding the Genetic and Phenotypic Spectrum of Female Infertility Caused by TUBB8 Mutations[J]. Reprod Sci, 2021, 28(12):3448-3457. doi: 10.1007/s43032-021-00694-0.
[9]	刁磊, 刘明一, 鲍岚. 微管蛋白亚型及其功能[J]. 中国细胞生物学学报, 2019, 41(3):321-332. doi: 10.11844/cjcb.2019.03.0001.
[10]	Feng R, Yan Z, Li B, et al. Mutations in TUBB8 cause a multiplicity of phenotypes in human oocytes and early embryos[J]. J Med Genet, 2016, 53(10):662-671. doi: 10.1136/jmedgenet-2016-103891.
[11]	Chen B, Wang W, Peng X, et al. The comprehensive mutational and phenotypic spectrum of TUBB8 in female infertility[J]. Eur J Hum Genet, 2019, 27(2):300-307. doi: 10.1038/s41431-018-0283-3.

[1]	ZHANG Dan-li, SHI Xue-dong, LI Jian-lei, ZHOU Li-fei, WANG Wen-yi, ZHANG Ping-ping, LI Ya-li. A Novel KMT2D Variant Causing Kabuki Syndrome [J]. Journal of International Reproductive Health/Family Planning, 2024, 43(6): 471-474.
[2]	JIANG Nan, ZHAO Xiao-li, LUAN Zu-qian, HUANG Zhi-yun, XIA Tian. Research Progress on the Correlation between Oxidative Stress and Aneuploidy in Oocytes of Aging Women [J]. Journal of International Reproductive Health/Family Planning, 2024, 43(5): 415-419.
[3]	LI Jia-li, TU Xu-xu, WANG Shi-meng, NIU Ding-ren, FENG Xiao-ling. Recurrent Spontaneous Abortion Related to Oxidative Stress at Maternal-Fetal Interface [J]. Journal of International Reproductive Health/Family Planning, 2024, 43(5): 435-440.
[4]	WU Chun-lei, ZHAO Xiao-li, QIU Yun-huan, WANG Bao-juan, DONG Rong, LI Kai-xi, XIA Tian. Integration of Gene Expression Microarrays and Single-Cell Transcriptomics to Identify Intercellular Communication in the Endometrium of Recurrent Implantation Failure Patients [J]. Journal of International Reproductive Health/Family Planning, 2024, 43(4): 265-273.
[5]	ZHUANG Qian-mei, LIU Chun-qiang, WANG Geng, YAN Mei-zhen, JIANG Yu-ying. Genetic Analysis of Two Cases of Rare α Thalassemia [J]. Journal of International Reproductive Health/Family Planning, 2024, 43(4): 302-304.
[6]	JIAO Meng-wen, ZHANG Yue-wen, WANG Ling, MO Shao-kang. Advances in CircRNAs Research in Reproductive System [J]. Journal of International Reproductive Health/Family Planning, 2024, 43(4): 322-327.
[7]	LIANG Yue, DONG Jie, XIAO Xi-feng, WANG Xiao-hong. Advancements of MiR-202 in Reproductive Modulation [J]. Journal of International Reproductive Health/Family Planning, 2024, 43(3): 228-233.
[8]	CAO Yuan-yuan, JIA Zan-hui, ZHANG Chun-miao. Research Progress of ZP1 Gene Mutation in Empty Follicle Syndrome [J]. Journal of International Reproductive Health/Family Planning, 2024, 43(2): 127-131.
[9]	TIAN Wen-yan, LUO Ying, LI Xiao-yan, YAN Qi, XUE Feng-xia, WANG Ying-mei, ZHANG Hui-ying. 45,X/47,XYY Disorders of Sex Development: A Case Report and Literature Review [J]. Journal of International Reproductive Health/Family Planning, 2024, 43(1): 11-16.
[10]	ZHANG Xiao-cui, YU Li-fei, YANG Yue-wei, LIU Yun-jing, HUANG Wei-dong, YI Jiang-yan, ZHANG Xue-ping. A Case of 45,X/46,XY Chromosomal Mosaic Infertility [J]. Journal of International Reproductive Health/Family Planning, 2024, 43(1): 20-23.
[11]	CUI Ling-bing, TIAN Wen-yan. SRY Negative 46, XX Male Syndrome with Normal Secondary Sexual Characteristics: A Case Report and Literature Review [J]. Journal of International Reproductive Health/Family Planning, 2023, 42(6): 454-456.
[12]	SHEN Ling-chao, WANG Xin, JI Dong-mei. Advances and Prevention Strategies for Mitochondrial Genetic Diseases Caused by the Mitochondrial DNA 8344A>G Mutation [J]. Journal of International Reproductive Health/Family Planning, 2023, 42(6): 471-475.
[13]	ZHANG Yu-jie, WANG Wen-cheng, ZHANG Ning. Research Progress of GDF-9 and BMP-15 on Follicular Development and Insulin Resistance in PCOS [J]. Journal of International Reproductive Health/Family Planning, 2023, 42(6): 487-491.
[14]	YE Ming-zhu, ZHENG Jie, LI Jie-peng, XU Li-xin. Application of Oocyte Cryopreservation in Patients with Iatrogenic Diminished Ovarian Reserve [J]. Journal of International Reproductive Health/Family Planning, 2023, 42(6): 498-502.
[15]	ZENG Lan, WANG Jin, ZHU Hui, WANG Qi-yan, ZHU Shu-yao, CHEN Ai, LUO Ze-min, PANG Ying. Clinical Manifestations and Genetic Analysis of 21 Cases with Aicardi-Goutières Syndrome [J]. Journal of International Reproductive Health/Family Planning, 2023, 42(5): 361-365.