RT Journal Article
SR Electronic
T1 Bi-allelic <em>SHOC1</em> loss-of-function mutations cause meiotic arrest and non-obstructive azoospermia
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 679
OP 686
DO 10.1136/jmedgenet-2020-107042
VO 58
IS 10
A1 Chencheng Yao
A1 Chao Yang
A1 Liangyu Zhao
A1 Peng Li
A1 Ruhui Tian
A1 Huixing Chen
A1 Ying Guo
A1 Yuhua Huang
A1 Erlei Zhi
A1 Jing Zhai
A1 Hongfang Sun
A1 Jianxiong Zhang
A1 Yan Hong
A1 Li Zhang
A1 Zhiyong Ji
A1 Feng Zhang
A1 Zhi Zhou
A1 Zheng Li
YR 2021
UL http://jmg.bmj.com/content/58/10/679.abstract
AB Background The genetic causes of human idiopathic non-obstructive azoospermia (NOA) with meiotic arrest remain unclear.Methods Two Chinese families with infertility participated in the study. In family 1, two brothers were affected by idiopathic NOA. In family 2, the proband was diagnosed with idiopathic NOA, and his elder sister suffered from infertility. Whole-exome sequencing (WES) was conducted in the two patients in family 1, the proband in family 2 and 362 additional sporadic patients with idiopathic NOA. Sanger sequencing was used to verify the WES results. Periodic acid–Schiff (PAS), immunohistochemistry (IHC) and meiotic chromosomal spread analyses were carried out to evaluate the stage of spermatogenesis arrested in the affected cases.Results We identified compound heterozygous loss of function (LoF) variants of SHOC1 (c.C1582T:p.R528X and c.231_232del:p.L78Sfs*9, respectively) in both affected cases with NOA from family 1. In family 2, homozygous LoF variant in SHOC1 (c.1194delA:p.L400Cfs*7) was identified in the siblings with infertility. PAS, IHC and meiotic chromosomal spread analyses demonstrated that the spermatogenesis was arrested at zygotene stage in the three patients with NOA. Consistent with the autosomal recessive mode of inheritance, all of these SHOC1 variants were inherited from heterozygous parental carriers. Intriguingly, WES of 362 sporadic NOA cases revealed one additional NOA case with a bi-allelic SHOC1 LoF variant (c.1464delT:p.D489Tfs*13).Conclusion To the best of our knowledge, this is the first report identifying SHOC1 as the causative gene for human NOA. Furthermore, our study showed an autosomal recessive mode of inheritance in the NOA caused by SHOC1 deficiency.Data are available on reasonable request. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.