Hereditary hearing loss: a 96 gene targeted sequencing protocol reveals novel alleles in a series of Italian and Qatari patients.

Deafness is a really common disorder in humans. It can begin at any age with any degree of severity. Hereditary hearing loss is characterized by a vast genetic heterogeneity with more than 140 loci described in humans but only 65 genes so far identified. Families affected by hearing impairment would have real advantages from an early molecular diagnosis that is of primary relevance in genetic counseling. In this perspective, here we report a family-based approach employing Ion Torrent DNA sequencing technology to analyze coding and UTR regions of 96 genes related to hearing function and loss in a first series of 12 families coming from Italy and Qatar. Using this approach we were able to find the causative gene in 4 out of these 12 families (33%). In particular 5 novel alleles were identified in the following genes LOXHD1, TMPRSS3, TECTA and MYO15A already associated with hearing impairment. Our study confirms the usefulness of a targeted sequencing approach despite larger numbers are required for further validation and for defining a molecular epidemiology picture of hearing loss in these two countries.

GJB2 and GJB6 genes and the A1555G mitochondrial mutation are only minor causes of nonsyndromic hearing loss in the Qatari population.

OBJECTIVE: This study reports results from the first survey of the genetic causes of nonsyndromic sensorineural hearing loss (NSHHL) in the Qatari population. DESIGN AND STUDY SAMPLES: Data were collected from 126 Qatari patients (58 males and 68 females) belonging to inbred families (56%), showing an autosomal recessive pattern of inheritance (96%). Fifty-three patients were less than 10 years old, 55 in the age range of 10 to 20 years, while 18 were aged between 20 and 30 years. All subjects had moderate to severe sensorineural hearing loss and were screened for GJB2 mutations, GJB6 deletion, and for A1555G mitochondrial mutation. RESULTS: Four patients were homozygous and one was heterozygous for c.35delG; five were homozygous for the IVS1 + 1G < A, and two were heterozygous for c.229 T > C. Only 8.3% of the pathogenic alleles were detected. No patients were positive for GJB6 deletion or for A1555G . CONCLUSIONS: These findings: (1) demonstrate that GJB2, GJB6 deletion and A1555G mutation account for a minor proportion of NSHHL in the Qatari population, (2) further strengthen the need to search for causative genes, (3) clearly contribute to establishing preventive strategies for NSHHL in Qatar and in the Gulf area.

Profile of stroke in Gizan, Kingdom of Saudi Arabia.

OBJECTIVE: The epidemiological characteristics of stroke at different geographical locations in the Kingdom of Saudi Arabia (KSA) have not been fully investigated. Reports from some areas indicate that stroke is one of the major causes of morbidity and mortality in the population. The present study was carried out to determine the clinical profile of stroke, its subtypes and associated risk factors in Gizan Province, KSA. METHODS: Data on consecutive patients with stroke admitted to King Fahd Central Hospital, Gizan, KSA over a 2-year period from January 1997 to December 1998, were retrospectively analyzed. Diagnosis was confirmed by computerized tomography of the brain. Etiologic and risk factors were identified by relevant clinical, laboratory and imaging investigations. RESULTS: Two hundred and forty-one patients (146 males and 95 females; mean age 64.5) were hospitalized during the study period. The subtypes of stroke comprised cerebral infarction (65.6%); intracerebral hemorrhage (30.7%) and sub-arachnoid hemorrhage (3.7%). Coma and convulsions were more frequent among patients with hemorrhagic strokes compared to the subgroup with cerebral infarction. Major risk factors included hypertension (45.6%), heart diseases with or without atrial fibrillation (31.1%) and diabetes mellitus (22.8%). In 19 (7.9%) patients, no risk factor was found. In-hospital mortality occurred in 20.3% (49 of 241 patients), with no significant difference in the rates in the different subtypes. CONCLUSION: The crude incidence (estimated as 15.9 per 100, 000) in Gizan, KSA, a largely rural area is lower than the reported rates in urban areas of KSA. However, intracerebral hemorrhage had a higher relative frequency, suggesting a geographic variation in the subtypes at different areas. The establishment of rehabilitation centers in the province will reduce the heavy burden on health services and relatives. The incidence and prevalence of stroke must be reduced by appropriate strategy with the objectives of preventing or modifying risk factors such as hypertension, diabetes mellitus and smoking. A national stroke registry should be strengthened to provide further information on the epidemiology of stroke in KSA.

Acoustic neuroma: outcome study.

Three therapeutic modalities have been advocated in the management of acoustic neuromas: observation, surgery, and radiosurgery. Although surgery is still considered conventional treatment, at times the management can be controversial. The objectives of this article are to assess the results of each of these treatment modalities in a tertiary care acoustic neuroma referral setting. The methodology chosen was to group the patients along the initial intent to treat and then to see the results obtained. A total of 51 patients followed in the Skull Base Clinic of the McGill University Health Centre were included. The intent to treat was as follows: observation, 22 patients; surgery, 26 patients; and radiosurgery, 3 patients. The results showed that 50% of those followed by observation demonstrated growth and required surgery or radiotherapy. Surgical results, in terms of facial nerve outcome, varied with tumour size but also improved dramatically with the introduction of facial nerve monitoring and a multidisciplinary approach. In small and medium-size tumours (< 30 mm), intent to treat by observation or by surgery (with intraoperative monitoring) yielded similar results. The limitations of this study are discussed. In the future, a prospective multicentric study may help better in assessing the value of the various management options.