A novel missense mutation in SMPX causes a rare form of X-linked postlingual sensorineural hearing loss in a Chinese family.

BACKGROUND: X-linked deafness-4 (DFNX4) caused by the functional loss of the SMPX gene is one form of nonsyndromic hearing loss with postlingual onset. This study aimed to investigate the cause of X-linked inherited sensorineural nonsyndromic hearing loss in a four-generation Chinese family and to explain the reason for extremely different hearing phenotypes between the proband and other family members. METHODS: Whole-exome sequencing (WES) and co-segregation analysis were used to identify the pathogenic variants. Furthermore, methylation differences among the androgen receptor genes were utilized to investigate whether the severe phenotype of the proband is related to X-chromosome inactivation (Xi). RESULTS: We described in detail the clinical characteristics of the family and identified a novel missense mutation (c.262C>G: p.Gln88Glu) in SMPX by WES. This variant was co-segregated with the postlingual hearing loss phenotype and was absent in 300 normal controls. Also, we found that the proband, a 4-year-old female, carries two new compound heterozygous mutations (c.9259G>A: p.Val3087Ile and c.8576G>A: p.Arg2859His) in the USH2A gene, but to date without any other symptoms except profound sensorineural hearing loss. Additionally, analysis of X-chromosome inactivation indicated moderate skewing in the proband, which is probably related to the heterogeneity of clinical characteristics. CONCLUSIONS: This is the first study to report a missense mutation of SMPX in a Chinese family. Our findings have enriched the mutation and phenotypic spectrum of the SMPX gene.

Does omethoate have the potential to cause insulin resistance?

Persistent organic pollutant exposure is strongly associated with the development of diabetes. The development of diabetes or alteration in blood glucose levels is associated with insulin resistance that precedes diabetes for many years. Omethoate is a commonly used insecticide in most developing countries. The present study was designed to elucidate the potent role of omethoate in developing insulin resistance in rats. Male Wistar rats were exposed to omethoate at the concentration of 1.5mg/kg body weight (1/40 LD50), 3 mg/kg body weight (1/20 LD50) and 6 mg/kg body weight (1/10 LD50) through gastric injection for 60 days; control group rats received PBS through gastric injection. The results showed that the levels of MDA, TNF-α and IL-6 were increased and the activities of SOD and GSH-Px were decreased in the right thigh muscles of rats exposed to omethoate. However, JNK, p38 MAPK and NF-κB in right thigh muscles of rats exposed to omethoate were activated. This study suggested that omethoate had a potential to cause insulin resistance.