Jiaxiong Wang1, Xiaoran Liu2, Ce Zhang1, Yongle Xu1, Weizhuo Wang1, Hong Li1, Shenmin Yang3, Jing Zhao4. 1. Center for Reproduction and Genetics, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, China. 2. Department of Reproductive Medicine Center, The First Affiliated Hospital of XinJiang Medical University, Urumqi, 830054, Xinjiang, China. 3. Center for Reproduction and Genetics, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, China. drim2004@126.com. 4. Department of Reproductive Medicine Center, The First Affiliated Hospital of XinJiang Medical University, Urumqi, 830054, Xinjiang, China. littlemili@126.com.
Abstract
PURPOSE: To investigate the potential genetic cause in a primary infertility patient with multiple morphological abnormalities of sperm flagella (MMAF). METHODS: The patient's sperm was observed by light and electron microscopy. Whole-exome sequencing (WES) was carried out to identify candidate genes. Then, the mutation found by WES was verified by Sanger sequencing. The proteins interacting with ARMC2 were revealed by co-immunoprecipitation (co-IP) and mass spectrometry. Intracytoplasmic sperm injection (ICSI) was carried out to achieve successful pregnancy. RESULTS: Typical MMAF phenotype (absent, short, coiled, bent irregular flagella) was shown in the patient's sperm. A novel homozygous mutation in ARMC2 (c.1264C > T) was identified. The proteins interacting with ARMC2 we found were CEP78, PGAM5, RHOA, FXR1, and SKIV2L2. The ICSI therapy was successful, and boy-girl twins were given birth. CONCLUSION: We found a novel mutation in ARMC2 which led to MMAF and male infertility. This is the first report of ICSI outcome of patient harboring ARMC2 mutation. The interacting proteins indicated that ARMC2 might be involved in multiple processes of spermatogenesis.
PURPOSE: To investigate the potential genetic cause in a primary infertility patient with multiple morphological abnormalities of sperm flagella (MMAF). METHODS: The patient's sperm was observed by light and electron microscopy. Whole-exome sequencing (WES) was carried out to identify candidate genes. Then, the mutation found by WES was verified by Sanger sequencing. The proteins interacting with ARMC2 were revealed by co-immunoprecipitation (co-IP) and mass spectrometry. Intracytoplasmic sperm injection (ICSI) was carried out to achieve successful pregnancy. RESULTS: Typical MMAF phenotype (absent, short, coiled, bent irregular flagella) was shown in the patient's sperm. A novel homozygous mutation in ARMC2 (c.1264C > T) was identified. The proteins interacting with ARMC2 we found were CEP78, PGAM5, RHOA, FXR1, and SKIV2L2. The ICSI therapy was successful, and boy-girl twins were given birth. CONCLUSION: We found a novel mutation in ARMC2 which led to MMAF and male infertility. This is the first report of ICSI outcome of patient harboring ARMC2 mutation. The interacting proteins indicated that ARMC2 might be involved in multiple processes of spermatogenesis.
Authors: André B Goncalves; Sarah K Hasselbalch; Beinta B Joensen; Sebastian Patzke; Pernille Martens; Signe K Ohlsen; Mathieu Quinodoz; Konstantinos Nikopoulos; Reem Suleiman; Magnus P Damso Jeppesen; Catja Weiss; Søren Tvorup Christensen; Carlo Rivolta; Jens S Andersen; Pietro Farinelli; Lotte B Pedersen Journal: Elife Date: 2021-07-14 Impact factor: 8.140