Molecular epidemiology of Usher syndrome in Italy.

PURPOSE: Usher syndrome is an autosomal recessive disorder characterized by hearing and vision loss. Usher syndrome is divided into three clinical subclasses (type 1, type 2, and type 3), which differ in terms of the severity and progression of hearing loss and the presence or absence of vestibular symptoms. Usher syndrome is defined by significant genetic heterogeneity, with at least 12 distinct loci described and 9 genes identified. This study aims to provide a molecular epidemiology report of Usher syndrome in Italy. METHODS: Molecular data have been obtained on 75 unrelated Italian patients using the most up-to date technology available for the screening of Usher syndrome gene mutations, i.e., the genotyping microarray developed by Asper Biotech (Tartu, Estonia), which simultaneously investigates 612 different marker positions using the well established arrayed primer extension methodology (APEX). RESULTS: Using this method, we found that 12% of cases (9 out of 75) harbored homozygous or compound heterozygous mutations in the gene positions analyzed, whereas 20% (15 out of 75) of the patients were characterized by the presence of only one mutated allele based on the positions analyzed. One patient was found to be compound heterozygous for mutations in two different genes and this represents an example of possible digenic inheritance in Usher syndrome. A total of 66.6% of cases (50 out of 75) were found to be completely negative for the presence of Usher syndrome gene mutations in the detected positions. Mutations detected by the array were confirmed by direct sequencing. CONCLUSIONS: These findings highlight the efficacy of the APEX-based genotyping approach in the molecular assessment of Usher patients, suggesting the presence of alleles not yet identified and/or the involvement of additional putative genes that may account for the pathogenesis of Usher syndrome.

Bilateral sudden profound hearing loss and vertigo as a unique manifestation of bilateral symmetric inferior pontine infarctions.

OBJECTIVES: We present a case of sudden bilateral profound deafness and vertigo, without any accompanying neurologic signs, secondary to bilateral infarctions of the cochlear and vestibular nuclei. METHODS: Vertigo, vomiting, tinnitus, and bilateral profound deafness suddenly developed in a 65-year-old woman without any accompanying neurologic signs. In particular, she did not present dysarthria, numbness, cranial nerve palsies, or visual or cerebellar signs. RESULTS: Magnetic resonance imaging of the brain revealed 2 fresh infarctions of 8 to 10 mm symmetrically localized in the posterolateral bulbopontine junction. Angiography revealed a complete occlusion of the basilar artery, with a well-represented backward flow of its distal portion from the carotid artery via posterior communicating arteries. Excluding a transient ischemic attack that occurred 16 days after the acute episode, the patient had had no other neurologic events at 8 months of follow-up. CONCLUSIONS: Acute vertigo and sudden deafness in a patient with known cerebrovascular occlusive disease may represent the warning signs of an impending brain stem or cerebellar infarction, even when other neurologic signs are absent. These events are fortunately very rare, but should be considered by clinicians who see patients with vertigo.

Symmetric sensorineural progressive hearing loss from chronic idiopathic pachymeningitis.

We present the case of a 68 year-old man with a diffused hypertrophic pachymeningitis (HP) involving both internal auditory canals. The clinical symptoms were headache, decreased vision in one eye, progressive bilateral and symmetrical sensory-neural hearing loss (PSNHL) responsive to steroid treatment. Although hearing loss is a frequent manifestation of HP, only few studies reported an adequate audiological assessment and follow-up. Mechanisms related to the auditory involvement are discussed on the basis of audiological data. Gadolinium enhanced MRI is the most adequate technique for HP detection and for the differential diagnosis. A delay in the diagnosis of HP seems to be quite common and the consequences may be severe, especially in cases of optic nerve involvement. For these reasons, a cerebral MRI should probably be included in the assessment of PSNHL, especially when neurological signs coexist or are reported in the medical history.

Human leukocyte antigen-A, -B, -C and -DR alleles and soluble human leukocyte antigen class I serum level in Ménière's disease.

Previous studies have suggested that many human leukocyte antigen (HLA)-A, -B, -C and -DR alleles are associated with Ménière's disease (MD), an inner ear disorder with a proposed autoimmune etiopathogenesis. Despite some discrepancies many reports are in agreement with a hypothesis suggesting an influence of serologically detected HLA-C products in the susceptibility to the disease. To confirm these data we investigated the distribution of HLA-A, -B, -C and -DR antigens that well define the HLA polymorphism using DNA typing. Furthermore, as autoimmune factors have been claimed to play a role in MD, we investigated the serum level of soluble HLA class I (sHLA-I). Molecular typing of HLA class I and II was performed using polymerase chain reaction sequence-specific primers in 41 patients affected by MD, 34 patients affected by other inner ear diseases (OIDs) and 101 healthy subjects. An ELISA technique was employed to investigate the serum level of sHLA-I in 17 MD patients, 10 OID patients and 83 healthy subjects. The results showed a significantly increased frequency of the Cw*07 specificities in MD patients when compared to OID patients (63.4% vs 32.3%; p = 6.9 x 10(-3); relative risk [RR] = 3.6) and healthy subjects (63.4% vs 35.6%; p = 2.28 x 10(-3); RR = 3.1). The sHLA-I concentrations detected in sera did not differ significantly between MD patients (616 +/- 271 ng/ml), OID patients (570 +/- 307 ng/ml) and healthy subjects (518 +/- 340 ng/ml).