Novel pathogenic WHRN variant causing hearing loss in a moroccan family.

OBJECTIVES: The most prevalent sensory disease in humans is deafness. A variety of genes have been linked to hearing loss, which can either be isolated (non-syndromic) or associated with lesions in other organs (syndromic). It has been discovered that WHRN variants are responsible for non-syndromic hearing loss and Usher syndrome type II. METHODS AND RESULTS: Exome sequencing in a consanguineous Moroccan patient with severe hearing loss identified a single homozygous mutation c.619G > T; p.Ala207Ser in WHRN, encoding a cytoskeletal scaffold protein that binds membrane protein complexes to the cytoskeleton in ocular photoreceptors and ear hair cell stereocilia. Bioinformatics methods and molecular dynamic modeling were able to predict the pathogenic implications of this variation. CONCLUSION: We used whole exome sequencing to find a homozygous WHRN gene variant in a Moroccan family. Numerous bioinformatics methods predict that this modification might result in a change in the WHRN protein's structure.

Melatonin is useful alternative for sedation in children undergoing auditory brainstem responses testing.

Auditory brainstem responses testing (ABRs) is frequently required to assess auditory function in children. It is done usually in outpatient fashion and requires deep sleep to avoid artefacts. Sedation method used for the test should allow a deep sleep while avoiding general anaesthesia that requires special monitoring, dedicated staff and operating room availability. For this purpose, several sedation methods have been used, with the risk of respiratory depression and sides effects. We aim to assess the efficacy and the usefulness of melatonin in sedation for children undergoing auditory brainstem responses testing. We calculated success rate of complete bilateral ABR, sleep delay and quality of sleep of 247 children referred for ABR testing. Two hundred six children (83.4%) successfully underwent both ears testing. The delay to sleep was variable with a mean of 32 min. The quality of sleep was described as continuous in 156 infants (75.7%) and discontinuous in 50 infants (24.27%) requiring either simple nursing or a second dose of melatonin 30 min later.Conclusion: Melatonin has the advantages of inducing natural sleep and reducing sleep delay without adverse effects or respiratory depression risk. It is efficient and useful sedation method for ABRs in an outpatient setting. What Is Known? • Auditory brainstem responses test is the most used objective test to assess auditory function in children and requires deep sleep to avoid artefacts. • Melatonin is an endogenous pineal hormone used for sedation in electrophysiological testing and magnetic resonance imaging. What Is New? • 83.4% of children in our study successfully performed a bilateral ABR under melatonin-induced sleep with continuous sleep in 75.7%. • The use of melatonin to induce sleep for ABR tests is useful in an outpatient setting and it is a good alternative to general anaesthesia in Morocco.

Further Evidence for the Implication of the MET Gene in Non-Syndromic Autosomal Recessive Deafness.

Mutations in the mesenchymal epithelial transition factor (MET) gene are frequently associated with multiple human cancers but can also lead to human non-syndromic autosomal recessive deafness (DFNB97). In the present study, we identified a novel homozygous missense mutation in the METgene causing a non-syndromic hearing impairment DFNB97 form. Whole-exome sequencing was performed to determine the genetic causes of hearing loss in a Moroccan consanguineous family with an affected daughter. The structural analysis of native and mutant in the SEMA domain of the MET receptor was investigated using a molecular dynamics simulation (MDS) approach. We identified a novel pathogenic homozygous c.948A>G (p.Ile316Met) mutation in the MET gene in one deaf Moroccan young girl carrying a total bilateral non-syndromic hearing impairment. The results of the MDS approach show that an Ile316Met mutation in the SEMA domain leads to protein flexibility loss. This may produce a major impact on the structural conformation of the MET receptor, which also affects the function and binding site of the receptor. This is the first time that a mutation in the MET gene is described in a Moroccan family. Moreover, this study reports the second family in the world associating deafness and mutation in the MET gene.

The Role of Surgery in the Treatment of Cervical Lymph Node Tuberculosis.

Cervical lymph node tuberculosis is a public health problem in Morocco and the rest of the world. Its paucibacillary nature makes diagnosis and treatment difficult. This is a descriptive-analytical retrospective study presenting 104 cases of patients with manifestations of cervical lymph node tuberculosis confirmed by pathological examination (100%), associated in some cases with positive bacteriology (40.6%), treated and followed up in the otolaryngology (ENT) department of the Cheikh Khalifa International University Hospital (HUICK) over a period of 5 years and 9 months (from January 01, 2017, to September 30, 2022). In our study, 14 patients (i.e., 13.5%) had a history of tuberculosis (all locations); only four (i.e., 3.8%) of them had confirmed cervical lymph node tuberculosis, of which three were still under treatment: two of them presented for treatment failure (i.e., 1.9%) and one patient for a paradoxical reaction (i.e., 1%). Three pulmonary locations (i.e., 2.9%) and one mediastinal location (i.e., 1%) were found. Surgery associated with histological study was the key to the diagnosis of tuberculosis in our study. Its procedures were: excisional biopsy for 26 patients (i.e., 25%), adenectomy for 54 patients (i.e., 51.9%), lymph node dissection for 15 patients (i.e., 14.4%), and lymphadenectomy for nine patients (i.e., 8.7%). In some cases, drainage (+/- curettage) was recommended in addition to the surgical procedure in 14 patients (i.e., 13.5%). All our patients benefited from post-surgical anti-bacillary treatment. Lymphorrhea was the only operative complication and it affected two patients (i.e., 1.9%). Meanwhile, the relapse rate was 10.6% (i.e., 11 patients), the treatment failure rate was 3.8% (i.e., four patients), and the paradoxical reaction affected 2.9% (i.e., three patients). The latter had all benefited from a simple biopsy. This indicates that a more extensive surgical procedure gives better results with a better healing rate. In conclusion, anti-bacillary treatment remains the reference treatment for lymph node tuberculosis. However, surgery holds great promise as the first-line treatment in case of fistula or abscess or in the event of failure or if complications occur.

A novel PEX1 mutation in a Moroccan family with Zellweger spectrum disorders.

Mutations in the PEX1 gene are usually associated with recessive inherited diseases including Zellweger spectrum disorders. In this work, we identified a new pathogenic missense homozygous PEX1 mutation (p.Leu1026Pro, c.3077T>C) in two Moroccan syndromic deaf siblings from consanguineous parents. This variation is located in the P-loop containing nucleoside triphosphate hydrolase of protein domain and probably causes an alteration in the hydrolysis of ATP.

Homozygous mutations in PJVK and MYO15A genes associated with non-syndromic hearing loss in Moroccan families.

OBJECTIVES: Autosomal recessive non-syndromic hearing loss is a heterogeneous disorder and the most prevalent human genetic sensorineural defect. In this study, we investigated the geneticcause of sensorineural hearing loss in Moroccan patients and presented the importance of whole exome sequencing (WES) to identify candidate genes in two Moroccan families with profound deafness. METHODS: After excluding mutations previously reported in Moroccan deaf patients, whole exome sequencing was performed and Sanger sequencing was used to validate mutations in these genes. RESULTS: Our results disclosed the c.113_114insT (p.Lys41GlufsX8) and c.406C > T (p.Arg130X) homozygous mutations in PJVK and a homozygous c.5203C > T (p.Arg1735Trp) mutation in MYO15A, both genes responsible for non-syndromic recessive hearing loss DFNB59 and DFNB3, respectively. CONCLUSION: We identified in Moroccan deaf patients two mutations in PJVK and one mutation in MYO15A described for the first time in association with non-syndromic recessive hearing loss. These results emphasize that whole exome sequencing is a powerful diagnostic strategy to identify pathogenic mutations in heterogeneous disorders with many various causative genes.

Update of the spectrum of GJB2 gene mutations in 152 Moroccan families with autosomal recessive nonsyndromic hearing loss.

Deafness is one of the most common genetic diseases in humans and is subject to important genetic heterogeneity. The most common cause of non syndromic hearing loss (NSHL) is mutations in the GJB2 gene. This study aims to update and evaluate the spectrum of GJB2 allele variants in 152 Moroccan multiplex families with non syndromic hearing loss. Seven different mutations were detected: c.35delG, p.V37I, p.E47X, p.G200R, p.Del120E, p.R75Q, the last three mutations were described for the first time in Moroccan deaf patients, in addition to a novel nonsense mutation, the c.385G>T which is not referenced in any database. Sixty six families (43.42%) have mutations in the coding region of GJB2, while the homozygous c.35delG mutation still to date the most represented 51/152 (33.55%). The analysis of the geographical distribution of mutations located in GJB2 gene showed more allelic heterogeneity in the north and center compared to the south of Morocco. Our results showed that the GJB2 gene is a major contributor to non syndromic hearing loss in Morocco. Thus, this report of the GJB2 mutations spectrum all over Morocco has an important implication for establishing a suitable molecular diagnosis.