Balkan Journal of Medical Genetics

COPY NUMBER VARIATIONS IN FEMALE INFERTILITY IN CHINA
Huang W*, Wang J, Pang M, Zhao Q, Kong L, Mao Y, Li W, Liang B
*Corresponding Author: Professor Weidong Huang, Reproductive Medicine Center, XinJiang JiaYin Hospital, 48 Nanhu North Road, Shuimogou District, Urumchi, Xinjiang Province, 830000, People’s Republic of China. Tel: +86-2363631402. Fax: +86-9914887187. E-mail: hwd@jynk.com
page: 5

DISCUSSION

This research showed the CNV preference for chromosome X in the 324 female infertility patients. The X chromosome is the key chromosome for female sexual organ development, and the long arm of the X chromosome was a key area of gonad development. The variation in chromosome X was prone to cause abnormal developments of gonad and infertility [17]. The presence of CNVs in the female genome may result in abnormalities in gamete formation and meiosis of oocyte, thereby influence fertility. One sample exhibited CNV on Xq21.1-q21.2, which involved a gene, POF1B. Loss of function in POF1B could lead to exaggerated germ cell apoptosis and POF [this gene included by the Online Mendelian Inheritance in Man (OMIM)], but this CNV was duplication instead of deletion [18,19]. Combined with clinical phenotype and female sex hormone levels detection, we believed that this CNV duplication may influence fertility. For CNV (9q22.32-q22.33) duplication, it contained HSD17B3 gene. The HSD17B3 gene mutations could impair testosterone bio-synthesis and causing male under masculinization [20], but its function has not been reported in females. For the rest of these CNVs, some contain protein coding genes related to diseases in the OMIM database, but they are mostly associated with other genetic disorders such as neuropathy, brain, skin and retina. Thus, the association between female infertility and CNVs are still unclear. Our data showed that CNVs may be not the main cause of unexplained infertility. In these 29 CNVs, there were five deletions and 24 duplications (Table 1). Our method cannot detect the inversions and translocations, which may lead to the low detection rate of the actual CNVs. We also found five recurring CNVs on Xp22.31, and three times on 22q11.21. The average size of Xp22.31 CNVs was about 1.6 M, including one deletion and four duplications. For clinical phenotypes, four patients with normal phenotype (sex hormone level and normal uterus), and one patient had one miscarriages and one spontaneous abortion. Xp22.31 contained the encoding genes of STS, VCX2, VCX, VCX3A, PNPLA4, HDHD1, etc. It was reported that the deletion, reduplication, and rearrangement of Xp22.31 can lead to X-linked ichthyosis. These five patients all showed no X-linked ichthyosis clinical phenotype. In 2010, Krausz et al. [21] found the CNVs on Xp22.31 for two male infertility patients. So far, there has been no report about Xp22.31 on female infertility. The Xp22.31 exhibits a frequency of 0.15% in a healthy population [22]. Thus, the correlation between Xp22.31 and female infertility needs to be further investigated. Three of the female infertility patients had CNVs on 22q11.21 duplications. The average size of Xp22.31 CNVs was about 2 M. The clinical phenotypes of these three patients were unexplained primary infertility, and their husbands exhibited normal sperm. The deletion CNV (22q11.21) was also found in two types I MRKH (Mayer- Rokitansky-Küster-Hauser) syndrome [14,23]. The association between 22q11.21 deletions and Müllerian aplasia has been reported [24,25]. Moreover, our patients have normal uterus and menstruation. There are many factors that influence female infertility including POF, leiomyomas, endometriosis and polycystic ovarian syndrome (PCOS), etc. For the first time, our study explored the correlation between CNVs and female infertility using NGS technology, and also provided genetic evidence and references for future study and infertility etiology research. Declaration of Interest. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. Funding. This study was supported by Natural Science funds of Xinjiang Uygur Autonomous Region [2017D01B10].

Number 27 VOL. 27 (2), 2024	Number 27 VOL. 27 (1), 2024
Number 26 Number 26 VOL. 26(2), 2023 All in one	Number 26 VOL. 26(2), 2023
Number 26 VOL. 26, 2023 Supplement	Number 26 VOL. 26(1), 2023
Number 25 VOL. 25(2), 2022	Number 25 VOL. 25 (1), 2022
Number 24 VOL. 24(2), 2021	Number 24 VOL. 24(1), 2021
Number 23 VOL. 23(2), 2020	Number 22 VOL. 22(2), 2019
Number 22 VOL. 22(1), 2019	Number 22 VOL. 22, 2019 Supplement
Number 21 VOL. 21(2), 2018	Number 21 VOL. 21 (1), 2018
Number 21 VOL. 21, 2018 Supplement	Number 20 VOL. 20 (2), 2017
Number 20 VOL. 20 (1), 2017	Number 19 VOL. 19 (2), 2016
Number 19 VOL. 19 (1), 2016	Number 18 VOL. 18 (2), 2015
Number 18 VOL. 18 (1), 2015	Number 17 VOL. 17 (2), 2014
Number 17 VOL. 17 (1), 2014	Number 16 VOL. 16 (2), 2013
Number 16 VOL. 16 (1), 2013	Number 15 VOL. 15 (2), 2012
Number 15 VOL. 15, 2012 Supplement	Number 15 Vol. 15 (1), 2012
Number 14 14 - Vol. 14 (2), 2011	Number 14 The 9th Balkan Congress of Medical Genetics
Number 14 14 - Vol. 14 (1), 2011	Number 13 Vol. 13 (2), 2010
Number 13 Vol.13 (1), 2010	Number 12 Vol.12 (2), 2009
Number 12 Vol.12 (1), 2009	Number 11 Vol.11 (2),2008
Number 11 Vol.11 (1),2008	Number 10 Vol.10 (2), 2007
Number 10 10 (1),2007	Number 9 1&2, 2006
Number 9 3&4, 2006	Number 8 1&2, 2005
Number 8 3&4, 2004	Number 7 1&2, 2004
Number 6 3&4, 2003	Number 6 1&2, 2003
Number 5 3&4, 2002	Number 5 1&2, 2002
Number 4 Vol.3 (4), 2000	Number 4 Vol.2 (4), 1999
Number 4 Vol.1 (4), 1998	Number 4 3&4, 2001
Number 4 1&2, 2001	Number 3 Vol.3 (3), 2000
Number 3 Vol.2 (3), 1999	Number 3 Vol.1 (3), 1998
Number 2 Vol.3(2), 2000	Number 2 Vol.1 (2), 1998
Number 2 Vol.2 (2), 1999	Number 1 Vol.3 (1), 2000
Number 1 Vol.2 (1), 1999	Number 1 Vol.1 (1), 1998

About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact