Efficacy and safety of medications for osteoporosis in kidney transplant recipients or patients with chronic kidney disease: A meta-analysis.

This study conducted a meta-analysis to analyze the efficacy and safety of osteoporosis medications in kidney transplant recipients and patients with chronic kidney disease (CKD). PubMed, Embase, the Cochrane Central Register of Controlled Trials were searched from the date of their inception through October 21, 2022. We performed a meta-analysis of the efficacy and safety of osteoporosis medications in adult patients with stage 3-5 CKD or kidney transplant recipients enrolled in randomized clinical trials (RCTs). We calculated the standard mean deviations with 95% confidence intervals (CI) for bone mineral density (BMD) and T scores after 6 and 12 months treatment, pooled odds ratio and 95% CI for fracture risk, and summarized adverse events. The inclusion criteria were met by 27 studies. Out of this, 19 studies were included for the meta-analysis. In stage 3-4 CKD patients, alendronate increased lumbar spine BMD. In patients at stage 5 CKD and undergoing hemodialysis, alendronate and raloxifene increased lumbar spine BMD. After 6 months, the BMD of kidney transplant recipients was seen to be significantly increased; however, there was no difference after 12 months, and the risk of fracture did not reduce. Thus, there is no evidence that these medications reduce the risk of fracture, and their effect on BMD and fracture remains unproven. These medications may increase the incidence of adverse events and their safety needs to be further evaluated. Therefore, we cannot draw a definitive conclusion about the efficacy and safety of osteoporosis medications in the above group of patients.

Short article: Sequence variations of PKHD1 underlie congenital hepatic fibrosis in a Chinese family.

OBJECTIVE: Congenital hepatic fibrosis (CHF) is a developmental disorder of the portobiliary system characterized by hepatic fibrosis, portal hypertension, and renal cystic disease. The aim of our study was to identify the disease-causing gene of a Chinese family with CHF. PATIENTS AND METHODS: Whole-exome sequencing was performed in the family with CHF and variants were confirmed by Sanger sequencing. Online bioinformatics tools were used to evaluate the pathogenicity of the missense variants. Liver specimens were reviewed to confirm the histopathological diagnosis. RESULTS: The compound heterozygous variants c.7994T>C, p.(Leu2665Pro) and c.8518C>T, p.(Arg2840Cys) in PKHD1 were identified in a Chinese family with CHF by whole-exome sequencing. Liver histomorphology was reviewed to confirm the diagnosis of CHF. CONCLUSION: We have identified variations in PKHD1 in a Chinese family with CHF. Our study extends the mutation spectrum of CHF and provides information for genetic counseling of patients' family members.

A novel missense mutation of CRYGS underlies congenital cataract in a Chinese family.

Congenital cataract is a clinically and genetically heterogeneous disease. In this study, we examined a five-generation Chinese family with autosomal dominant nuclear congenital cataracts by whole exome sequencing. A novel heterozygous missense mutation c.199T>A, p.(Tyr67Asn) in CRYGS was identified in this family. The p.(Tyr67Asn) substitution was predicted to decrease the local hydrophobicity and affect the three-dimensional structure of γS-crystallin, and resulted in a portion of mutant protein translocation from the cytoplasm to cell membrane. Our observations expand the mutation spectrum of CRYGS and provide further evidence for the genetic basis and molecular mechanism of congenital cataract.

Clinical and genetic characteristics of Chinese patients with familial or sporadic pediatric cataract.

BACKGROUND: Pediatric cataract is a clinically and genetically heterogeneous disease which is a significant cause of lifelong visual impairment and treatable blindness. Our study aims to investigate the genotype spectrum in a group of Chinese patients with pediatric cataract. METHODS: We enrolled 39 families with pediatric cataract from October 2015 to April 2016. DNA samples of the probands were analyzed by target next-generation sequencing. Variants were validated using Sanger sequencing in the probands and available family members. RESULTS: In our cohort of 39 cases with different types of pediatric cataract, 23 cases were found to harbor putative pathogenic variants in 15 genes: CRYAA, CRYBA1, CRYBA4, CRYBB1, CRYGC, CRYGD, MIP, GCNT2, IARS2, NHS, BCOR, BFSP2, FYCO1, MAF, and PAX6. The mutation detection rates in the familial and sporadic cases were 75 and 47.8%, respectively. Of the 23 causative variants, over half were novel. CONCLUSIONS: This is a rare report of systematic mutation screening analysis of pediatric cataract in a comparably large cohort of Chinese patients. Our observations enrich the mutation spectrum of pediatric cataract. Next-generation sequencing provides significant diagnostic information for pediatric cataract cases, especially when considering sporadic and subtle syndromal cases.

Mutations in mevalonate pathway genes in patients with familial or sporadic porokeratosis.

Porokeratosis comprises heterogeneous keratinization disorders that are characterized by one or more atrophic patches surrounded by a ridge-like cornoid lamella. In this study, we evaluated seven families affected by porokeratosis and five sporadic patients of the disease in a Chinese population. We performed Sanger sequencing of exons and flanking intron-exon boundaries of mevalonate pathway genes (MVD, MVK, PMVK and FDPS) and of SLC17A9. In five familial and three sporadic patients, we detected six variations, including four novel mutations (MVD c.1A>G; p.Met1?, c.916G>A; p.Ala306Thr, c.1013+1G>A, and PMVK c.65A>G; p.Lys22Arg) and two recurrent mutations (MVD c.746T>C; p.Phe249Ser, and MVK c.1028T>C; p.Leu343Pro). We then applied I-TASSER and iGEMDOCK to assess these variants for probable functional impacts. The findings of this study extend the mutation spectrum of porokeratosis and provide further evidence for the genetic basis of this disease.

A missense mutation of HOXA13 underlies hand-foot-genital syndrome in a Chinese family.

Hand-foot-genital syndrome (HFGS) is a rare autosomal dominant inherited syndrome characterized by limb malformations and urogenital defects. HFGS is caused by mutations in the HOXA13 gene. The aim of this study was to identify causative mutations in individuals and to explore the molecular pathogenesis in a Chinese family with HFGS. We performed Sanger sequencing and identified a recurrent missense mutation in the homeodomain (c.1123G>T, p.V375F) of HOXA13, molecular modelling predicted the mutation would affect DNA binding, and a luciferase reporter assay indicated that it impaired the ability of HOXA13 to activate transcription of the human EPHA7 promoter. This is the first report of the molecular basis for HFGS caused by missense mutations of HOXA13.