RT Journal Article SR Electronic T1 DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP jmedgenet-2017-104992 DO 10.1136/jmedgenet-2017-104992 A1 Wen-Bin He A1 Chao-Feng Tu A1 Qiang Liu A1 Lan-Lan Meng A1 Shi-Min Yuan A1 Ai-Xiang Luo A1 Fu-Sheng He A1 Juan Shen A1 Wen Li A1 Juan Du A1 Chang-Gao Zhong A1 Guang-Xiu Lu A1 Ge Lin A1 Li-Qing Fan A1 Yue-Qiu Tan YR 2018 UL http://jmg.bmj.com/content/early/2018/01/13/jmedgenet-2017-104992.abstract AB Background The genetic causes of the majority of male and female infertility caused by human non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) with meiotic arrest are unknown.Objective To identify the genetic cause of NOA and POI in two affected members from a consanguineous Chinese family.Methods We performed whole-exome sequencing of DNA from both affected patients. The identified candidate causative gene was further verified by Sanger sequencing for pedigree analysis in this family. In silico analysis was performed to functionally characterise the mutation, and histological analysis was performed using the biopsied testicle sample from the male patient with NOA.Results We identified a novel homozygous missense mutation (NM_007068.3: c.106G>A, p.Asp36Asn) in DMC1, which cosegregated with NOA and POI phenotypes in this family. The identified missense mutation resulted in the substitution of a conserved aspartic residue with asparaginate in the modified H3TH motif of DMC1. This substitution results in protein misfolding. Histological analysis demonstrated a lack of spermatozoa in the male patient’s seminiferous tubules. Immunohistochemistry using a testis biopsy sample from the male patient showed that spermatogenesis was blocked at the zygotene stage during meiotic prophase I.Conclusions To the best of our knowledge, this is the first report identifying DMC1 as the causative gene for human NOA and POI. Furthermore, our pedigree analysis shows an autosomal recessive mode of inheritance for NOA and POI caused by DMC1 in this family.