Assisted reproduction outcomes for patients with multiple morphological abnormalities of the sperm flagella caused by CFAP43 or CFAP44 gene mutations
Geng Hao, Tang Dongdong, Wu Huan, Duan Zongliu, Li Kuokuo, Xu Chuan, Lyu Mingrong, He Xiaojin
Abstract
ObjectiveTo investigate the clinical outcomes of patients with multiple morphological abnormalities of the flagella (MMAF) caused by CFAP43 or CFAP44 gene mutations following intracytoplasmic sperm injection (ICSI).
MethodsClinical data and genetic information were retrospectively analyzed for 121 MMAF patients who attended Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University during September 2014 to July 2020. Totally 9 MMAF patients were identified to carry CFAP43 or CFAP44 mutations, 5 of them (P3, P5, P7, P8, and P9) received ICSI treatments, the ICSI outcomes were further analyzed.
ResultsSanger sequencing validated 9 MMAF patients harboring CFAP43 or CFAP44 biallelic mutations, our study firstly identified a novel homozygous mutation of CFAP43(c.4132delC: p.Arg1378Glufs*10), novel compound heterozygous mutations of CFAP43 (c.3938G>A: p.Arg1313Gln;c.4342G>A:p.Glu1448Lys) and novel compound heterozygous mutations ofCFAP44 (c.1718C>A:p.Pro573His; c.4075G>A: p.Glu1359Lys). The 5 MMAF patients underwent 5 ICSI cycles, 4 healthy offspring were obtained. The rate of fertilization ofCFAP43- or CFAP44-mutated MMAF patients following ICSI was 76.47% (39/51), 3 patients' wife got clinical pregnancy, 3 patients got live birth delivery, respectively. No significant differences were found in ICSI outcomes among CFAP43-mutated or CFAP44-mutated MMAF patients, DNAH1-mutated MMAF patients, and severe oligoasthenozoospermia group (all P>0.05).
ConclusionCFAP43 or CFAP44 mutations are responsible for the malformation of sperm flagella and decrease of sperm motility, and validated as the important genetic causes of MMAF. CFAP43- or CFAP44-mutated MMAF patients could have a favorable treatment outcome following ICSI.
Key words:
Sperm injection, intracytoplasmic; Whole exome sequencing; CFAP43; CFAP44; Multiple morphological abnormalities; Assisted reproduction outcomes
Contributor Information
Geng Hao
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Anhui Province Key Laboratory of Reproductive Health and Genetics, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China
Tang Dongdong
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Anhui Province Key Laboratory of Reproductive Health and Genetics, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China
Wu Huan
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Anhui Province Key Laboratory of Reproductive Health and Genetics, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China
Duan Zongliu
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Anhui Province Key Laboratory of Reproductive Health and Genetics, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China
Li Kuokuo
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Anhui Province Key Laboratory of Reproductive Health and Genetics, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China
Xu Chuan
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Anhui Province Key Laboratory of Reproductive Health and Genetics, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China
Lyu Mingrong
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Anhui Province Key Laboratory of Reproductive Health and Genetics, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China
He Xiaojin
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Anhui Province Key Laboratory of Reproductive Health and Genetics, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China
