BackgroundCongenital cataract, a kind of cataract presenting at birth or during early childhood, is a leading cause of childhood blindness. To date, more than 30 genes on different chromosomes are known to cause this disorder. This study aimed to identify the HSF4 mutations in a cohort from Chinese families affected with congenital cataracts.MethodsForty-two unrelated non-syndromic congenital cataract families and 112 ethnically matched controls from southeast China were recruited from the southeast of China. We employed Sanger sequencing method to discover the variants. To confirm the novel mutations, STR haplotypes were constructed to check the co-segregation with congenital cataract. The pathogenic potential of the novel mutations were assessed using bioinformatics tools including SIFT, Polyphen2, and Human Splicing Finder. The pathogenicity of all the mutations was evaluated by the guidelines of American College of Medical Genetics and InterVar software.ResultsNo previously reported HSF4 mutations were found in all the congenital cataract families. Five novel HSF4 mutations including c.187 T > C (p.Phe63Leu), c.218G > T (p.Arg73Leu), c.233A > G (p.Tyr78Cys), IVS5 c.233-1G > A and c.314G > C (p.Ser105Thr) were identified in five unrelated families with congenital cataracts, respectively. These mutations co-segregated with all affected individuals in each family were not observed in the unaffected family members or in 112 unrelated controls. All five mutations were categorized to be the disease “pathogenic” according to ACMG guidelines and using InterVar software. Mutations in the HSF4 were responsible for 11.90% Chinese families with congenital cataracts in our cohort.ConclusionsIn the study, we identified five novel HSF4 mutations in Chinese families with congenital cataracts. Our results expand the spectrum of HSF4 mutations causing congenital cataracts, which may be helpful for the molecular diagnosis of congenital cataracts in the era of precision medicine.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0636-3) contains supplementary material, which is available to authorized users.

The currently used anti-cytokine therapeutic antibodies cannot selectively neutralize pathogenic cytokine signalling that cause collateral damage to protective signalling cascades. The single domain chain firstly discovered in Camelidae displays fully functional ability in antigen-binding against variable targets, which has been seemed as attractive candidates for the next-generation biologic drug study. In this study, we established a simple prokaryotic expression system for a dual target-directed single domain-based fusion protein against the interleukin-6 receptor and human serum, albumin, the recombinant anti-IL-6R fusion protein (VHH-0031). VHH-0031 exhibited potent anti-inflammatory effects produced by LPS on cell RAW264.7, where the major cytokines and NO production were downregulated after 24 h incubation with VHH-0031 in a dose-dependent manner. In vivo , VHH-0031 presented significant effects on the degree reduction of joint swelling in the adjuvant-induced arthritis (AIA) rat, having a healthier appearance compared with the dexamethasone. The expression level of JNK protein in the VHH-0031 group was significantly decreased, demonstrating that VHH-0031 provides a low-cost and desirable effect in the treatment of more widely patients.

The currently used anti-cytokine therapeutic antibodies cannot selectively neutralize pathogenic cytokine signalling that cause collateral damage to protective signalling cascades. The single domain chain firstly discovered in Camelidae displays fully functional ability in antigen-binding against variable targets, which has been seemed as attractive candidates for the next-generation biologic drug study. In this study, we established a simple prokaryotic expression system for a dual target-directed single domain-based Fusion Protein against the interleukin-6 receptor and human serum, albumin, the recombinant anti-IL-6R fusion protein (VHH-0031). VHH-0031 exhibited potent anti-inflammatory effects produced by LPS on cell RAW264.7, where the major cytokines and NO production were down-regulated after 24 hr incubation with VHH-0031 in a dose-dependent manner. In vivo, VHH-0031 presented significant effects on the degree reduction of joint swelling in the adjuvant-induced arthritis (AIA) rat, having a healthier appearance compared to the dexamethasone. The expression level of JNK protein in the VHH-0031 group was significantly decreased, demonstrating that VHH-0031 provides a low-cost and desirable effect in the treatment of more widely patients.