Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population.

Usher syndrome type I (USH1), the most severe form of this syndrome, is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. At least seven USH1 loci, USH1A-G, have been mapped to the chromosome regions 14q32, 11q13.5, 11p15, 10q21-q22, 21q21, 10q21-q22, and 17q24-25, respectively. Mutations in five genes, including MYO7A, USH1C, CDH23, PCDH15 and SANS, have been shown to be the cause of Usher syndrome type 1B, type 1C, type 1D, type 1F and type 1G, respectively. In the present study, we carried out a systematic mutation screening of these genes in USH1 patients from USA and from UK. We identified a total of 27 different mutations; of these, 19 are novel, including nine missense, two nonsense, four deletions, one insertion and three splicing defects. Approximatelly 35-39% of the observed mutations involved the USH1B and USH1D genes, followed by 11% for USH1F and 7% for USH1C in non-Acadian alleles and 7% for USH1G. Two of the 12 MYO7A mutations, R666X and IVS40-1G > T accounted for 38% of the mutations at that locus. A 193delC mutation accounted for 26% of CDH23 (USH1D) mutations, confirming its high frequency. The most common PCDH15 (USH1F) mutation in this study, 5601-5603delAAC, accounts for 33% of mutant alleles. Interestingly, a novel SANS mutation, W38X, was observed only in the USA cohort. The present study suggests that mutations in MYO7A and CDH23 are the two major components of causes for USH1, while PCDH15, USH1C, and SANS are less frequent causes.

The effects of improving hearing in dementia.

BACKGROUND: audiological function is impaired in people with dementia and poor hearing is known to exaggerate the effects of cognitive deficits. OBJECTIVE: the objective of this study was to assess the effects of increasing auditory acuity by providing hearing aids to subjects with dementia who have mild hearing loss. METHOD: subjects were screened for hearing impairment and fitted with a hearing aid according to standard clinical practice. Measures of cognition and psychiatric symptoms, activities of daily living, and burden on carers were made over 6 months. Hearing aid diaries were kept to record the acceptability of the hearing aids to the subjects. RESULTS: more than 10% of eligible subjects were excluded as removal of wax restored hearing. Subjects showed a decline in cognitive function, no change in behavioural or psychiatric symptoms over the study period. Forty-two percent of subjects showed an improvement on an independently rated measure of change. The hearing aids were well accepted. Both carers and subjects reported overall reduction in disability from hearing impairment. CONCLUSIONS: all patients with hearing impairment require thorough examination. The presence of dementia should not preclude assessment for a hearing aid as they are well tolerated and reduce disability caused by hearing impairment. Hearing aids do not improve cognitive function or reduce behavioural or psychiatric symptoms. There is evidence that patients improved on global measures of change.