OBJECTIVE: To explore the genetic etiology of fetal skeletal dysplasia using whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) techniques, and the feasibility of using WES as the first-tier method for such fetuses. METHODS: Seventy four fetuses with skeletal dysplasia detected by prenatal ultrasound at the Genetic Testing Center of the Women and Children's Hospital Affiliated to Qingdao University from January 2020 to August 2024 were selected as the study subjects. Fetal muscle and peripheral blood samples of the pregnant women and their spouses were collected and subjected to WES analysis. CNV-seq was carried out on all fetal muscle tissue samples. And the results were compared with the CNVs indicated by WES. Genetic etiologies were analyzed across different subtypes of skeletal dysplasia. And the feasibility of using WES as the first-tier genetic test for similar fetuses was assessed, in addition with a systematic cost-effectiveness analysis. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: QFELL-YJ-2024-201). RESULTS: A total of 50 fetuses were diagnosed, which yielded a diagnostic rate of 67.57%. These included 6 chromosomal aneuploidies, 4 chromosomal CNVs and 40 monogenic disorders. The monogenic diseases had involved 46 variant sites in 23 pathogenic genes, among which 12 were unreported previously, including MYH3: c.735T>C, ALPL: c.1324C>T, NEK9: c.1973G>A, MAGEL2: c.2024_2025del, LMBR1: c.423+4914A>C, NEB: c.21273_21276del, COL1A1: c.2651G>C and c.2758G>C, ASPM: c.2473delinsGA, TBX5: c.704G>A, DYNC2H1: c.10893del, and DYNC2I2: c.1270C>T. Substantial concordance was reached between WES-derived CNV calls and CNV-seq findings. No clinically significant CNV was exclusively detected by CNV-seq. Cost-effectiveness modeling demonstrated that implementing WES as the first-tier genetic testing method could reduce the total expenditure when WES unit cost remained below 6.4 folds that of the CNV-seq. CONCLUSION Genetic variants including single nucleotide variations (SNV) of monogenic disorders, chromosomal aneuploidies and genomic CNVs are important causes for fetal skeletal dysplasia. WES is an accurate and efficient method for analyzing the etiology of fetal skeletal dysplasia, particularly in those with a family history of similar phenotype or maternal history of adverse pregnancies.
Humans ; Exome Sequencing/methods* ; Female ; Pregnancy ; DNA Copy Number Variations/genetics* ; Genetic Testing/methods* ; Prenatal Diagnosis/methods* ; Adult ; Male ; Fetus ; Bone Diseases, Developmental/diagnosis* ; Ultrasonography, Prenatal

Objective To study the protection of glutathione (GSH) on renal oxidative damage to mice which caused by mi‐crocystin‐LR(MC‐LR) .Methods Forty healthy KM mice were divided into five groups by randomly sampling ,which were saline control group ,GSH control group ,MC‐LR group ,low dose GSH +MC‐LR group and high dose GSH +MC‐LR group ,and the ex‐periment was lasting 15 days by intraperitoneal injection .Then we took out the kidney for pathological observation and detected the activity of CAT ,SOD ,GSH‐Px and the content of GSH ,MDA .Results Compared with control group ,the MC‐LR increased the content of MDA[(2 .31 ± 0 .22)nmol/mg prot ,P=0 .000] and decreased the content of GSH[(0 .68 ± 0 .02)mg/g prot] .The activi‐ty of CAT[(320 .54 ± 38 .99)nmol/mg prot] ,SOD[(180 .93 ± 15 .30)U/mg prot] ,GSH‐Px[(295 .11 ± 42 .40)U/mg prot](P<0 .05) .However ,after GSH was given ,compared with MC‐LR group ,MDA content[(1 .94 ± 0 .12)nmol/mg prot]of high dose GSH+MC‐LR group significantly decreased (P<0 .05) ,GSH content[(1 .01 ± 0 .08)mg/g prot ,(1 .08 ± 0 .16)mg/g prot]and CAT activity[(383 .46 ± 21 .98)nmol/mg prot ,(428 .50 ± 28 .61)nmol/mg prot] of both GSH groups significantly increased (P<0 .05) ,the activity of SOD[(222 .01 ± 11 .51)U/mg prot] and GSH‐Px[(358 .37 ± 20 .29)U/mg prot] of high dose GSH +MC‐LR group significantly increased (P<0 .05) .Conclusion MC‐LR may cause renal oxidative damage through promoting the lipid perox‐idation on renal cells .The GSH may reach a certain protective effect on kidney by reducing the lipid peroxidation ,improving the an‐tioxidant activity ,and removing oxygen free radicals .