Compound heterozygosity for dominant and recessive GJB2 mutations in a Tunisian family and association with successful cochlear implant outcome

Objectives

Mutations of GJB2 encoding connexin 26 are the most common cause of hearing loss. They are responsible for up to 50% of ARNSHL. The pathogenic mutations in this gene are generally inherited recessively. Dominant mutations in GJB2 also cause hearing loss, either in isolated non-syndromic form or as part of a syndrome associated with various skin disorders.

Methods

We screened a Tunisian child affected by congenital, bilateral, profound, sensorineural hearing loss for mutations in GJB2 gene using PCR and direct sequencing.

Results

The proband was found to be compound heterozygous for recessive and dominant GJB2 mutations respectively p.V37I (c.109G > A) and p.R143Q (c.428G > A). Surprisingly the hearing mother is a carrier for this dominant GJB2 mutation. This proband underwent a cochlear implant at four years old. The evaluation using APCEI and IT-MAIS tests at six months post implantation indicates a successful cochlear implant outcome since the deaf child began to acquire language abilities and auditory sensation.

Conclusions

The p.R143Q mutation was described for the first time in Tunisia. We confirm the low penetrance of this mutation since the proband mother is a carrier despite her normal hearing. We show the effectiveness of cochlear implant to restore the communication abilities and auditory sensation for our patient.     

Splenogonadal fusion misdiagnosed as spermatic cord cyst: a case report

Introduction Splenogonadal fusion is a rare congenital anomaly. The aim of this study was to report a case of splenogonadal fusion mimicking a spermatic cord cyst, and discuss therapeutic management of this rare congenital malformation. Observation An eight-years old patient was presented with an asymptomatic three-centimeter oval scrotal mass mistaken for a spermatic cord cyst. Surgical exploration has revealed tow purple-red, firm encapsulated masses. The first mass was two cm long and adherent to the upper pole of the left testis with a cleavage plane. The second mass was four cm long, attached to the first by a fibrous cord and drawn on its superior pole by a serpiginous vascular structure that extended inside the abdomen. The spermatic cord was individualized. Extemporaneous anatomopathological examination of the first mass, totally excised, has concluded to benign lesion. Therefore, the peritoneum was opened, and the superior mass was excised as high as it could be reached without orchiectomy. Definitive Anatomopathological examination concluded to an ectopic splenic tissue. The final diagnosis was a continuous splenogonadal fusion. Conclusion This case highlights the clinical characteristics of this condition, with a special focus on the signs and findings that might help prevent unnecessary orchiectomy. Consequently, it is essential to include this malformation in the differential diagnosis of scrotal masses in children.     

Genome‐wide association study of psoriasis in an Egyptian population

Psoriasis is a chronic inflammatory disorder of the skin, with genetic factors reportedly involved in the disease pathogenesis. Numerous studies reported psoriasis candidate genes. However, these tend to involve mostly in the European and Asian populations. Here, we report the first genome‐wide association study (GWAS) in an Egyptian population, identifying susceptibility variants for psoriasis using a two‐stage case‐control design. In the first discovery stage, we carried out a genome‐wide association analysis using the Infinium^® Global Screening Array‐24 v1.0, on 253 cases and 449 control samples of Egyptian descent. In the second replication stage, 26 single‐nucleotide polymorphisms (SNPs) were selected for replication in additional 321 cases and 253 controls. In concordance with the findings from previous studies on other populations, we found a genome‐wide significant association between the MHC locus and the disease at rs12199223 (P_comb = 6.57 × 10^?18) and rs1265181 (P_comb = 1.03 × 10^?10). Additionally, we identified a novel significant association with the disease at locus, 4q32.1 (rs12650590, P_comb = 4.49 × 10^?08) in the vicinity of gene GUCY1A3, and multiple suggestive associations, for example rs10832027 (P_comb = 7.28 × 10^?06) and rs3770019 (P_comb = 1.02 × 10^?05). This proposes the existence of important interethnic genetic differences in psoriasis susceptibility. Further studies are necessary to elucidate the downstream pathways of the new candidate loci.     

Distal renal tubular acidosis in a Libyan patient: Evidence for digenic inheritance

Aim of the study

Recent advances in understanding the underlying molecular mechanism for distal renal tubular acidosis (dRTA), led to an increased attention towards the primary and the familial forms of the disease. Mutations in ATP6V1B1 and ATP6V0A4 are usually responsible for the recessive form of the disease. Mutations in gene AE1 encoding the Cl-/HCO3- exchanger, usually present as dominant dRTA, but a recessive pattern has been recently described. Our objective is to identify the mutational spectrum responsible of dRTA in a consanguineous Libyan family.

Neurobehavioral assessment following e-cigarette refill liquid exposure in adult rats

The present study was conducted to assess the toxic effect of e-cigarette refill liquid on cognitive and motor functions in adult rats. Animals were administered 28?μl/kg of body weight of e-liquid with/without a dose of 0.5?mg of nicotine/kg of body weight, using the intraperitoneally route for a period of 4 weeks. They were then evaluated by novel object recognition test (NORT) and spontaneous alternation T-maze test for cognitive functions. Results indicated that e-liquid without nicotine induced, in the NORT, a decrease in time exploring the novel object during the test session and lower discrimination and recognition indexes compared to control and e-liquid with nicotine treated rats. Furthermore, short-term spatial memory was affected after e-liquid treatment in the spontaneous alternation T-maze test, identifying recognition memory impairments. However, none of the treatments altered motor functions assessed by inclined plane test, Kondziela’s inverted screen test and weights test. Cell cytotoxicity assessment following e-liquid exposure showed a significant decrease in hippocampal cell viability, but no change in cortical cell viability. Thereby, e-liquid without nicotine causes cognitive impairments, especially on the hippocampus. Based on these results, more extensive assessments on e-cigarettes must be carried out.     

Impact of e-cigarette refill liquid with or without nicotine on liver function in adult rats

This study was conducted to evaluate the effects of e-cigarette refill liquid administration alone or with nicotine on the antioxidant defense status, functional and histopathological changes in adult rat liver tissue. For this purpose, 32 rats were treated for 28 days as follows: control group was injected intra-peritoneally with physiological saline; e-cigarette 0% treated group received an intra-peritoneal injection of e-liquid without nicotine diluted in physiological saline, e-cigarette-treated group received an intra-peritoneal injection of e-liquid containing 0.5?mg of nicotine/kg of body weight/day diluted in physiological saline and nicotine-treated group received an intra-peritoneal injection of 0.5?mg of nicotine/kg of body weight/day diluted in physiological saline. In e-liquid without nicotine-exposed group, activities of the liver biomarkers aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase increase. Interestingly, oxidative stress indicators showed decreased total protein content, associated with a reduction in the antioxidant enzymes activities superoxide dismutase, catalase and glutathione-S-transferase, and an elevation in malondialdehyde content, highlighting the promotion of lipid peroxidation and oxidative stress. Histological studies identified inflammatory cells infiltration and cell death. Thus, e-liquid seems to promote oxidative tissue injuries, which in turn lead to the observed histopathological finding. In comparison, nicotine alone induced less oxidative stress and less histopathological disorders, whereas e-liquid with nicotine gave rise to more histopathological injuries. Thereby, e-liquid, per se, is able to induce hepatotoxicity and supplementation with nicotine worsens this state.     

Development of novel polymer-stabilized diosmin nanosuspensions: In vitro appraisal and ex vivo permeation

Scanty solubility and permeability of diosmin (DSN) are perpetrators for its poor oral absorption and high inter-subject variation. This article investigated the potential of novel DSN nanosuspensions to improve drug delivery characteristics. Bottom-up nanoprecipitation technique has been employed for nanosuspension development. Variables optimized encompassed polymeric stabilizer type, DSN: stabilizer ratio, excess stabilizer removal, spray drying, and mannitol incorporation. In vitro characterization included particle size (PS), infrared spectroscopy (IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), transmission electron microscope (TEM), scanning electron microscopy (SEM), and dissolution profile. Ex vivo permeation was assessed in rats using non-everted sac technique and HPLC. Optimal DSN nanosuspension (DSN:hydroxypropylmethyl cellulose HPMC 2:1) was prepared with acid base neutralization technique. The formula exhibited the lowest PS (336 nm) with 99.9% drug loading and enhanced reconstitution properties after mannitol incorporation. SEM and TEM revealed discrete, oval drug nanocrystals with higher surface coverage with HPMC compared to MC. DSN nanosuspension demonstrated a significant enhancement in DSN dissolution (100% dissolved) compared to crude drug (51%). Permeation studies revealed 89% DSN permeated from the nanosuspension after 120 min compared to non-detected amounts from drug suspension. Conclusively, novel DSN nanosuspension could successful improve its dissolution and permeation characteristics with promising consequences of better drug delivery.