Novel in-frame deletion mutation c.177_179del TAC of neurofibromatosis type 1 in a Chinese 4-year-old boy with binocular blindness

Dear editor,I am Dr.Jie Peng,from the Department of Ophthalmology,Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai,China.I write to present a case report of a novel in-frame deletion mutation c.177179del TAC of neurofibromatosis type 1 in a Chinese boy with bilateral blindness.Neurofibromatosis type 1（NF1;OMIM#162200）,an autosomal dominant disease,is caused by mutations in the NF1gene.The incidence of this disease is around 1 in

Correlation between the Insertion/Deletion Mutations of Prion Protein Gene and BSE Susceptibility and Milk Performance in Dairy Cows

Objective To investigate the 23 bp and 12 bp insertion/deletion(indel)mutations within the bovine prion protein(PRNP)gene in Chinese dairy cows,and to detect the associations of two indel mutations with BSE susceptibility and milk performance.Methods Based on bovine PRNP gene sequence,two pairs of primers for testing the 23 bp and 12 bp indel mutations were designed.The PCR amplification and agarose electrophoresis were carried out to distinguish the different genotypes within the mutations.Moreover,based on previous data from other cattle breeds and present genotypic and allelic frequencies of two indels mutations in this study,the corrections between the two indel mutations and BSE susceptibility were tested,as well as the relationships between the mutations and milk performance traits were analyzed in this study based on the statistical analyses.Results In the analyzed Chinese Holstein population,the frequencies of two"del"alleles in 23 bp and 12 bp indel muations were more frequent.The frequency of haplotype of 23del-12del was higher than those of 23del-12ins and 23ins-12del.From the estimated r2and D’values,two indel polymorphisms were linked strongly in the Holstein population(D’=57.5%,r2=0.257).Compared with the BSE-affected cattle populations from the reported data,the significant differences of genotypic and allelic frequencies were found among present Holstein and some BSE-affected populations(P<0.05 or P<0.01).Similarly,there were significant frequency distribution differences of genotypes and alleles among Chinese Holstein and several previous reported healthy dairy cattle(P<0.05 or P<0.01).Moreover,association of genotype and combined genotypes of two indel polymorphisms with milk performance and resistant mastitis traits were analyzed in Holstein population,but no significant differences were found(P>0.05).Conclusions These observations revealed that the influence of two indel mutations within the bovine PRNP gene on BSE depended on the breed and they did not affect the milk production traits,which layed the foundation for future selection of resistant animals,and for improving health conditions for dairy breeding against BSE in China.

SOD2 Alleviates Hearing Loss Induced by Noise and Kanamycin in Mitochondrial DNA4834-deficient Rats by Regulating PI3K/MAPK Signaling

Superoxide dismutase 2(SOD2)-mediated gene therapy has significant protective effects against kanamycin-induced hearing loss and hair cell loss in the inner ear,but the underlying mechanisms are still unclear.Herein,an in vivo aging model of mitochondrial DNA(mtDNA)4834 deletion mutation was established using D-galactose,and the effects of noise or kanamycin on inner ear injury was investigated.Rats subjected to mtDNA4834 mutation via D-galactose administration showed hearing loss characterized by the disruption of inner ear structure(abnormal cell morphology,hair cell lysis,and the absence of the organ of Corti),increased SOD2 promoter methylation,and an increase in the degree of apoptosis.Exposure to noise or kanamycin further contributed to the effects of D-galactose.SOD2 overexpression induced by viral injection accordingly counteracted the effects of noise and kanamycin and ameliorated the symptoms of hearing loss,suggesting the critical involvement of SOD2 in preventing deafness and hearing-related conditions.The PI3K and MAPK signaling pathways were also regulated by noise/kanamycin exposure and/or SOD2 overexpression,indicating that they may be involved in the therapeutic effect of SOD2 against age-related hearing loss.

Analysis of Type Ⅱ Toxin-Antitoxin Genes all 3211-asl3212 in Anabaena PCC 7120

The type Ⅱ toxin-antitoxin genes are responsible for the phenotypic switch to a quasi-dormant state that enables cell survival under stresses,a similar function to heterocyst of cyanobacteria. In this paper,we particularly study the role of gene pair all3211-asl3212 under Spectinomycin stress to reveal how the type Ⅱ toxin-antitoxin involved in environmental stress responses. Bioinformatics prediction shows that toxin protein gene All3211 is homologous to Maz F,a member of maz EF family that encoding nucleases. We clone gene all3211-asl3212 into expression vectors to identify its molecular characteristics. Deletion mutant strains of all3211-asl3212 are selected in a tri-parental mating screen. Phenotype comparisons of mutant and wild type reveals no difference of single-deletion-mutants in pigment integrity,the sensitivity to antibiotics,and heterocyst formation. The results show that deletion mutation of single TAS gene pair all3211-asl3212 results in limited effects on the cellular growth of PCC 7120. Thus,we suggest that dosage compensating might be provided from redundant genes or bypass pathways to offset obvious phenotypic differences.