title: Whole-exome sequencing identified a homozygous BRDT mutation in a patient with acephalic spermatozoa.
abstract: Acephalic spermatozoa is a very rare disorder of male infertility. Here, in a patient from from a consanguineous family, we have identified, by whole-exome sequencing, a homozygous mutation (c.G2783A, p.G928D) in the BRDT gene. The gene product, BRDT, is a testis-specific protein that is considered an important drug target for male contraception. The G928D mutation is in the P-TEFb binding domain, which mediates the interaction with transcription elongation factor and might affect the transcriptional activities of downstream genes. By RNA-sequencing analysis of cells expressing the BRDT mutation, we found the p.G928D mutation protein causes mis-regulation of 899 genes compared with BRDT wild-type cells. Furthermore, by Gene Ontology analysis, the upregulated genes in p.G928D cells were enriched in the processes of intracellular transport, RNA splicing, cell cycle and DNA metabolic process, revealing the underlying mechanism of the pathology that leads to acephalic spermatozoa.
authors.affiliation: Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Reproductive Medicine Center, Xiamen Maternal and Child Health Care Hospital, Xiamen, 361005, Fujian Province, China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Sha
authors.affiliation: Center for Genetics, National Research Institute for Family Planning, Haidian, Beijing, 100081, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Reproductive Medicine Center, Xiamen Maternal and Child Health Care Hospital, Xiamen, 361005, Fujian Province, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China.
authors.forename: Kehkooi
authors.initials: K
authors.lastname: Kee
authors.affiliation: Center for Genetics, National Research Institute for Family Planning, Haidian, Beijing, 100081, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003241:Consanguinity; D059472:Exome / Q000235:genetics*; D005192:Family Health; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D063990:Gene Ontology; D006720:Homozygote; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008854:Microscopy, Electron; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D013094:Spermatozoa / Q000002:abnormalities / Q000648:ultrastructure; D000092468:Bromodomain Containing Proteins
chemical_list: D009687:Nuclear Proteins; C109570:BRDT protein, human; D000092468:Bromodomain Containing Proteins
keywords: BRDT; RNA-sequencing; acephalic spermatozoa; mutation; whole-exome sequencing