الفهرس 
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Abstract
Hearing impairment is the most frequent neurosensory deficit in human. Deafness is a clinically and genetically heterogeneous disorder with many known genetic and environmental causes. Hereditary hearing loss is a heterogeneous group of genetic entities, which can be distinguished by their clinical manifestations, mode of inheritance and genetic locus.
Hearing loss may be either syndromic (associated with external ear malformations or manifestations in other organs or systems) or non-syndromic (isolated deafness with no other medical problems). Approximately 60–70% of non-syndromic cases show a recessive pattern of inheritance, 20–30% of cases show dominant transmission and 2–3% are X-linked. Also, mutations in mitochondrial DNA (mtDNA) play an important role in the genetic causes of deafness.
The A1555G mutation in the mitochondrial 12S rRNA gene is one of the common causes of sensorineural hearing loss and aminoglycoside-induced deafness. It was the first mtDNA mutation identified as a cause of maternally inherited non-syndromic HL, and it has been implicated in aminoglycoside associated HL. Phenotypic expression of mutation A1555G is extremely variable, including cases of normal hearing carriers. Hearing loss, in affected cases, shows a varied age of onset and severity, some individuals being deaf from birth, whereas others show a slow, progressive hearing loss of adult-onset.
The A1555G mutation was found in various ethnic groups from Europe, Asia and Africa, with a variable prevalence. To our knowledge, there are no available data regarding the involvement of the mtDNA mutations in pathogenesis of deafness in Egypt.
The aim of the work is to search for the A1555G mutation among patients with non-syndromic sensorineural hearing loss, which will allow accurate diagnosis and better genetic counseling since the maternal relatives of patients with the A1555G mutation will be at risk for aminoglycoside induced deafness. The work will also include a study of the A1555G mutation among a sample of the Egyptian population to estimate the local population prevalence.
The study was conducted on 97 patients from 76 families. They were diagnosed with bilateral sensorineural hearing loss. These patients were recruited from the Audiology Unit at the Otorhinolaryngology Department, Alexandria University Main Hospital. Moreover, patients referred to the Genetic clinic at the Human Genetics Department, Medical Research Institute, Alexandria University for genetic counseling were also included. Healthy 300 individuals with normal hearing were also included as a control group in the study.
All patients were subjected to detailed history taking including the medical, genetic and family history, pedigree construction, clinical evaluation, and assessment of peripheral hearing sensitivity. Patients, available relatives and the control group were subjected to molecular genetic testing using PCR-RFLP technique to detect A1555G mutation.
The results of this study revealed the following:
(i) The age of the studied patients ranged from 1 month to 65 years with the mean age 6.2years. About 68% of them are affected preschool children.
(ii) Males represent about 47.4% of the studied patients. Females were 52.6%. Male to female ratio was 1:1.1.
(iii) The majority of the studied patients (95.9%) were complaining of prelingual sensorineural hearing loss.
(iv) Parental consanguinity among the studied families was 46% with first cousin marriages (28.3%).
(v) Fifty eight patients (59.8%) were isolated (sporadic cases); meanwhile thirty nine patients (40.2%) were familial.
(vi) All patients were only suffering from non-syndromic sensorineural hearing loss.
(vii) Aminoglycosides exposure wasn’t reported in any patient’s history.
(viii) Variable degrees of hearing loss were reported: 6.2% of the patients were affected with moderately severe SNHL, 60.8% with severe SNHL and 33% with profound SNHL.
(ix) One patient (1.3%) out of 76 index patients (probands) was found to be carrying the mutation. He is the offspring of non-consanguineous marriage with no family history of sensorineural hearing loss. No history of prior exposure to aminoglycosides was reported. Hearing loss was prelingual profound bilateral and sensorineural. None of the maternal relatives of the affected proband were carrying the A1555G mutation.
(x) None of the control group showed positive results.