الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 64 |  |  |
| | | from | 64 | | |
Abstract
Hearing loss is the most common sensory disorder in humans. Congenital hearing loss affects approximately 1 to 3 in 1000 live births in the general population, and 50%-60% of these cases have genetic etiologies. Non-syndromic deafness is responsible for about 70% of the genetic deafness cases. The autosomal recessive mode of inheritance is the most common form detected in approximately 77% of the patients.
Mutations in one single gene, GJB2 on DFNB1 locus on 13q, which encodes the Cx 26 protein, explains more than 50% of non-syndromic recessive hearing loss cases in most populations worldwide. The 35delG mutation is the most common mutation in the Caucasians and may cause up to 70% of all GJB2gene mutations. The 167delT mutation is the most common in affected Ashkenazi Jews.
Undoubtedly, the study of GJB2 gene has greatly contributed to the elucidation of the etiology of deafness, and as a consequence, diagnosis and genetic counseling have improved.
This study aimed to detect (35delG and 167delT) mutations in the Cx 26 gene among patients with non-syndromic SNHL. This will allow accurate diagnosis, more effective management, proper genetic counseling and carrier detection.
The present study was conducted on 54 patients (from 43 families) referred to the Genetic Clinic, Human Genetic Department, Medical Research Institute from the Audiology Unit, Otorhinolaryngology Department, Faculty of Medicine, Alexandria University and from private clinics in Alexandria.
Selection criteria of the deaf patients included in the study: patients with bilateral, pre-lingual, non-syndromic, sensorineural hearing loss, with no definite known acquired etiology as infections, teratogens, acoustic trauma or any other neonatal disease and no age or gender limit.
The study group was subjected to careful history taking, clinical genetic examination, assessment of peripheral hearing sensitivity, and other investigations that were done when suspecting syndromic hearing loss. After exclusion of 3 patients from 3 families discovered of having syndromic deafness during the clinical assessment, 51 patients from 40 families were enrolled in the molecular study using PSDM for 35delG mutation detection and PCR/RFLP technique for detection of the 167delT.
The results of this study revealed the following:
• Seven cases had the 35delG mutation (7/51, 13.7%). Four patients were homozygous and 3 patients were heterozygous for the deletion. Two homozygotes for this mutation were sibs and 2 heterozygotes were sibs as well. The allelic frequency for 35delG was 10.8% (11 out of 102 investigated alleles in 51 patients).
• The seven 35delG homozygote and heterozygote subjects were affected with severe to profound SNHL. These 7 cases were detected within the 17 patients suffering from severe to profound SNHL (41.2%).
• All the 7 homozygous and heterozygous35delG patients were born to consanguineous parents.
• The 35delG homozygous patients were two male and two female patients. The 35delG heterozygous patients were three females.
• Regarding the deaf patients homozygous for the deletion: all their normally hearing parents were identified to be heterozygous carriers for the 35delG. In one family, a normally hearing maternal aunt was a carrier for 35delG. In another family, a normally hearing sib was not a carrier.
• As regards the deaf patients heterozygous for the deletion: the parents in one family refused to be subjected to molecular testing. In the other family, the normally hearing mother was identified to be a heterozygous carrier for the 35delG while the normally hearing father was not a carrier.
• The 167delT mutation wasn’t detected in any of the studied patients.