Mohan Liu1,2, Jinhui Li3, Chuan Jiang1, Yanning Zhou4, Yongkang Sun1, Yihong Yang5, Ying Shen6. 1. Department of Obstetrics/Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, China. 2. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, 610041, China. 3. Department of Neonatology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, China. 4. School of Life Sciences, Sichuan Agricultural University, Ya'an, 625014, China. 5. Reproduction Medical Center of West China Second University Hospital, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, 610041, China. yyhpumc@foxmail.com. 6. Department of Obstetrics/Gynecology, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, China. yingcaishen01@163.com.
Abstract
PURPOSE: To evaluate the unknown genetic causes of teratozoospermia, and determine the pathogenicity of candidate variants. METHODS: A primary infertile patient and his family members were recruited in the West China Second University Hospital of Sichuan University. Whole-exome sequencing was performed to identify causative genes in a man with teratozoospermia. Immunofluorescence staining and western blotting were applied to assess the pathogenicity of the identified variant. Intracytoplasmic sperm injection (ICSI) was used to assist fertilization for the patient with teratozoospermia. RESULTS: We performed whole-exome sequencing (WES) and detected a novel homozygous frameshift mutation of c.335_336del [p.E112Vfs*3] in DNAJB13 on a primary infertile male patient. Intriguingly, we identified abnormal sperm morphology in this patient, with recurrent respiratory infections and chronic cough. Furthermore, we confirmed that this mutation resulted in negative effects on DNAJB13 expression in the spermatozoa of the affected individual, causing ultrastructural defects in his sperm. Remarkably, our staining revealed that DNAJB13 was expressed in the cytoplasm of primary germ cells and in the flagella of spermatids during spermiogenesis in humans and mice. Finally, we are the first group to report a favorable prognosis using ICSI for a patient carrying this DNAJB13 mutation. CONCLUSION: Our study revealed a novel homozygous frameshift mutation of c.335_336del [p.E112Vfs*3] in DNAJB13 involved in teratozoospermia phenotype. Our study greatly expands the spectrum of limited DNAJB13 mutations, and is expected to provide a better understanding of genetic counseling diagnoses and subsequent treatment of male infertility.
PURPOSE: To evaluate the unknown genetic causes of teratozoospermia, and determine the pathogenicity of candidate variants. METHODS: A primary infertile patient and his family members were recruited in the West China Second University Hospital of Sichuan University. Whole-exome sequencing was performed to identify causative genes in a man with teratozoospermia. Immunofluorescence staining and western blotting were applied to assess the pathogenicity of the identified variant. Intracytoplasmic sperm injection (ICSI) was used to assist fertilization for the patient with teratozoospermia. RESULTS: We performed whole-exome sequencing (WES) and detected a novel homozygous frameshift mutation of c.335_336del [p.E112Vfs*3] in DNAJB13 on a primary infertile male patient. Intriguingly, we identified abnormal sperm morphology in this patient, with recurrent respiratory infections and chronic cough. Furthermore, we confirmed that this mutation resulted in negative effects on DNAJB13 expression in the spermatozoa of the affected individual, causing ultrastructural defects in his sperm. Remarkably, our staining revealed that DNAJB13 was expressed in the cytoplasm of primary germ cells and in the flagella of spermatids during spermiogenesis in humans and mice. Finally, we are the first group to report a favorable prognosis using ICSI for a patient carrying this DNAJB13 mutation. CONCLUSION: Our study revealed a novel homozygous frameshift mutation of c.335_336del [p.E112Vfs*3] in DNAJB13 involved in teratozoospermia phenotype. Our study greatly expands the spectrum of limited DNAJB13 mutations, and is expected to provide a better understanding of genetic counseling diagnoses and subsequent treatment of male infertility.
Authors: Heike Olbrich; Karsten Häffner; Andreas Kispert; Alexander Völkel; Andreas Volz; Gürsel Sasmaz; Richard Reinhardt; Steffen Hennig; Hans Lehrach; Nikolaus Konietzko; Maimoona Zariwala; Peadar G Noone; Michael Knowles; Hannah M Mitchison; Maggie Meeks; Eddie M K Chung; Friedhelm Hildebrandt; Ralf Sudbrak; Heymut Omran Journal: Nat Genet Date: 2002-01-14 Impact factor: 38.330
Authors: H Omran; K Häffner; A Völkel; J Kuehr; U P Ketelsen; U H Ross; N Konietzko; T Wienker; M Brandis; F Hildebrandt Journal: Am J Respir Cell Mol Biol Date: 2000-11 Impact factor: 6.914
Authors: Elias Elinati; Paul Kuentz; Claire Redin; Sara Jaber; Frauke Vanden Meerschaut; Joelle Makarian; Isabelle Koscinski; Mohammad H Nasr-Esfahani; Aygul Demirol; Timur Gurgan; Noureddine Louanjli; Naeem Iqbal; Mazen Bisharah; Frédérique Carré Pigeon; H Gourabi; Dominique De Briel; Florence Brugnon; Susan A Gitlin; Jean-Marc Grillo; Kamran Ghaedi; Mohammad R Deemeh; Somayeh Tanhaei; Parastoo Modarres; Björn Heindryckx; Moncef Benkhalifa; Dimitra Nikiforaki; Sergio C Oehninger; Petra De Sutter; Jean Muller; Stéphane Viville Journal: Hum Mol Genet Date: 2012-05-31 Impact factor: 6.150