Genetic analysis of three cases of acephalic spermatozoa syndrome caused by SUN5 mutation and the outcome of assisted reproductive technology / 北京大学学报(医学版)

To explore the genetic causes of 3 male infertility patients with acephalospermia and the outcome of assisted reproductive technology. Clinical diagnosis, sperm morphology examination, sperm transmission electron microscopy examination were performed on 3 patients, and the whole exome sequencing technology was used for screening, Sanger sequencing verification, mutation pathogenicity analysis, and protein sequence homology comparison. Assisted reproductive technology was implemented to assist pregnancy treatment. The 3 patients were all sporadic infertile men, aged 25, 42 and 26 years, and there was no obvious abnormality in the general physical examination. Male external genitalia developed normally, bilateral testicles were normal in volume, and bilateral epididymis and spermatic vein were palpated without nodules, cysts, and tenderness. Repeated semen analysis showed that a large number of immature sperm could be seen, and they had the ability to move. The SUN5 gene of the 3 male infertile patients was a case of homozygous missense mutation c.7C>T (p.Arg3Trp), a case of compound heterozygous missense mutation c.1067G>A (p.Arg356His) and nonsense mutation c.216G>A (p.Trp72*) and a case of homozygous missense mutation c.1043A>T (p.Asn348Ile), of which c.7C>T (p.Arg3Trp) and c.1067G>A (p.Arg356His) were new variants that had not been reported. SIFT, Mutation Taster and PolyPhen-2 software function prediction results were all harmful, the nonsense mutation c.216G>A (p.Trp72*) led to the premature termination of peptide chain synthesis which might have a greater impact on protein function. The homology regions in the protein sequence homology alignment were all highly conserved.The 3 male patients and their spouses obtained 4 biological offspring through intracytoplasmic sperm injection, all of which were boys, and one of them was a twin.Three male infertile patients might be caused by SUN5 gene mutations. Such patients could obtain their biological offspring through assisted reproductive technology. It was still necessary to pay attention to the genetic risk of ASS, it was recommended that both men and women conduct genetic counseling and screening at the same time. In clinical diagnosis, whole exome sequencing technology could be used to perform auxiliary examinations to determine the treatment plan and assisted reproductive methods as soon as possible to reduce the burden on the family and society. The newly discovered mutation sites of SUN5 gene provided clues and directions for elucidating the pathogenic mechanism, and at the same time expanded the pathogenic mutation spectrum of ASS.

Three New Triterpenoid Saponins from Notoginseng Medicinal Fungal Substance.

Three new triterpenoid saponins, named ginsenoside-Rh23 (1), ginsenoside-Rh24 (2), and ginsenoside-Rh25 (3), were isolated from notoginseng medicinal fungal substance. Their structures were elucidated by a combination of 1D- and 2D-NMR, MS and chemical analysis. Compounds 1 - 3 exhibited moderate cytotoxic activity against MCF-7 and NCI-H460 cancer cell lines.

Estimation of genomic inbreeding coefficients based on high-density SNP markers in Chinese Holstein cattle.

In livestock, inbreeding coefficient based on pedigree information is usually used to evaluate the level of inbreeding. Recently, with cost reduction of high-density SNP genotyping, it's possible to analyze real genomic inbreeding degree using genomic information. In this study, utilizing high-density SNP chip data, we analyzed the frequency and distribution of runs of homozygosity (ROH) in 2107 Chinese Holstein cattle in Beijing area, and calculated 2 genomic inbreeding coefficients, i.e., 1) the proportion of ROH length in the total length of autosomal genome (Froh), and 2) the percentage of homozygous SNPs (Fhom). Then we analyzed the correlation between 2 genomic inbreeding coefficients and the correlation between genomic and pedigree inbreeding coefficients. We totally detected 44 676 ROHs that mainly ranged from 1 to 10 Mb. Various lengths of ROHs existed in the genome. There were more short ROHs than long ROHs. ROHs aren't evenly distributed in chromosomes. The area with most ROHs is in the middle part of chromosome 10. Strong correlation (r > 0.90) existed between 2 kinds of genomic inbreeding coefficients, but the correlation between pedigree and genomic inbreeding coefficients were much lower (r < 0.50). Our finding suggests that pedigree completeness influences the correlation between genomic and pedigree inbreeding. Genomic inbreeding measures may reflect individuals' real inbreeding, which could be a useful tool to evaluate population inbreeding.