Mutations in the gamma-actin gene (ACTG1) are associated with dominant progressive deafness (DFNA20/26).

Age-related hearing loss (presbycusis) is a significant problem in the population. The genetic contribution to age-related hearing loss is estimated to be 40%-50%. Gene mutations that cause nonsyndromic progressive hearing loss with early onset may provide insight into the etiology of presbycusis. We have identified four families segregating an autosomal dominant, progressive, sensorineural hearing loss phenotype that has been linked to chromosome 17q25.3. The critical interval containing the causative gene was narrowed to approximately 2 million bp between markers D17S914 and D17S668. Cochlear-expressed genes were sequenced in affected family members. Sequence analysis of the gamma-actin gene (ACTG1) revealed missense mutations in highly conserved actin domains in all four families. These mutations change amino acids that are conserved in all actins, from protozoa to mammals, and were not found in >100 chromosomes from normal hearing individuals. Much of the specialized ultrastructural organization of the cells in the cochlea is based on the actin cytoskeleton. Many of the mutations known to cause either syndromic or nonsyndromic deafness occur in genes that interact with actin (e.g., the myosins, espin, and harmonin). The mutations we have identified are in various binding domains of actin and are predicted to mildly interfere with bundling, gelation, polymerization, or myosin movement and may cause hearing loss by hindering the repair or stability of cochlear cell structures damaged by noise or aging. This is the first description of a mutation in cytoskeletal, or nonmuscle, actin.

Audiologic aspects of the search for DFNA20: a gene causing late-onset, progressive, sensorineural hearing loss.

OBJECTIVE: The purpose of this research was to identify the gene responsible for a novel form of nonsyndromic, late-onset, bilateral, progressive, sensorineural hearing loss in a Michigan family of English descent. This report describes the audiologic aspects of the search. DESIGN: Fifty-eight members of the family served as subjects for the study. Family pedigree information was gathered from family interviews, family records, birth and death registration records and census data. Audiologic evaluation was used to describe the hearing loss (phenotype) and classify family members as affected or unaffected based on hearing status. These data then were used in a linkage analysis, a process in which the inheritance of a trait is compared with the inheritance of genetic markers and statistically significant associations are sought. RESULTS: The team mapped the hearing loss to the long arm of chromosome 17 at band 17q25. The pattern of inheritance is autosomal dominant. The search for the gene is continuing using a candidate gene approach. CONCLUSIONS: The hearing loss demonstrated by this mid-Michigan family is a novel form of nonsyndromic, genetic, late-onset, bilateral, progressive, sensorineural hearing loss. The locus of the gene, the 20th for autosomal dominant hearing loss, is at band 17q25 of chromosome 17.

A new locus for late-onset, progressive, hereditary hearing loss DFNA20 maps to 17q25.

We report the localization of DFNA20, a gene causing dominant, nonsyndromic, progressive hearing loss in a three-generation Midwestern family, to chromosome 17q25. Affected family members show a bilateral, sloping, progressive, sensorineural hearing loss, first evident at 6000 and 8000 Hz, that can be identified in some family members in the early teens and is clearly evident by the early twenties. As age increases, the degree of hearing loss increases with threshold shifts seen at all frequencies. Linkage to known hereditary hearing loss loci was excluded. A genome-wide screen detected positive linkage to D17S784 (LOD(Z) = 6.62; θ = 0). Haplotype analysis refines the DFNA20 critical region to 12 cM between D17S1806 and D17S668. Radiation hybrid mapping with Stanford G3 and TNG panels was used to evaluate the genes ACTG1, GRIN2C, FKHL13, P4HB, SPARC, and ARHGDIA as candidates for DFNA20.

Beginning signers' self-assessment of sign language skills.

Students enrolled in introductory manual communication classes demonstrated limited ability to assess their own communication skills. Questionnaires completed on the third day of class revealed that 70% of the students surveyed would attempt to interpret in a court of law if asked to do so. Although a fifty-minute discussion concerning topics such as ASL, sign systems, and interpreter skills and ethics aided some students in putting their skills into perspective, 41% continued to overestimate their abilities at midterm. The reasons for the overestimation are not clear. Avenues for future research are suggested.

Deriving passage difficulties for a tracking study via the Cloze technique.

The current report demonstrates the importance of formally accounting for passage difficulty when using the tracking procedure. Cloze responses to 82 encyclopedia excerpts (343-349 words each) were obtained from a large pool of normal-hearing adults and scored verbatim. Passage difficulty, derived via ANOVA, was then defined as the deviation of a passage's mean Cloze score from the score for all passages, corrected for differences among respondents. The passage difficulties were applied in an alternating conditions tracking experiment with one adult cochlear implant user. Conditions included conventional auditory-visual and auditory-only tracking and experimental mode-switching techniques in which the talker changed modalities during the correction phase. An ANCOVA of the word-per-minute scores was conducted, with passage difficulty as a covariate and passage adjustment values as the output. Tracking rates and percentage of words correct from the beginning and end of training were examined. Use of adjusted data reversed the interpretation of performance change, demonstrating the need for determining passage difficulties a priori.

Oral communication skills of children who are hard of hearing.

Forty children with mild to severe hearing losses were administered a battery of speech and language tasks. The children's speech was characterized by misarticulation of affricates and fricatives, mild-moderate hoarseness, mild resonance problems, and good intelligibility. Their language samples included syntactic errors, primarily involving the use of bound morphemes and complex sentence structures. The children's pragmatic errors consisted primarily of providing inadequate or ambiguous information to the listener. These results indicate a consistent pattern of oral communication behavior that reflects the reduction of acoustic input that they experience.

Communication strategies of adult cochlear implant candidates.

Adult cochlear implant candidates' abilities to cope with communication breakdown were assessed using the Communication Strategies Task (CST). Forty adult cochlear implant candidates with acquired hearing losses and 10 adults with normal hearing served as subjects. Appropriateness of responses to the CST were rated by 10 certified speech-language pathologists and audiologists. Seventy-six percent of the subjects demonstrated difficulty identifying onset or resolution of communication breakdown, communicators' feelings, factors contributing to communication breakdown, and appropriate repair strategies. The responses of individuals with sudden hearing losses did not differ significantly from the responses of individuals with progressive hearing losses. Response patterns did not correlate with the age of onset of the hearing loss, duration of deafness, age at the time of evaluation, or educational background. The results of this study suggest that ability to cope with communication breakdown must be evaluated on an individual basis.

Monitoring Preschoolers' Hearing Aids: Issues in Program Design and Implementation.

Review of data obtained from a small sample of parents of preschoolers indicates that although most parents are aware of the need to monitor hearing aids for signs of malfunction, they do not always have the equipment and the skills needed to accomplish the task. Information from studies of physician/parent and audiologist/parent relationships provides a foundation for examining the problem. Data from these sources suggest that marked changes may be possible if clinicians change the ways they interact with parents.

Measuring the effects of head and neck support systems on signals transmitted to the ear.

Some individuals with motor control problems require head and/or neck support systems to achieve proper positioning in their wheelchairs. Signal transmission to a KEMAR positioned in a wheelchair with three commonly used support systems was evaluated with a probe microphone system. The three systems created different patterns of shadow and baffle effects. Audiologists are advised to evaluate the acoustic impact of the specific support systems used by their patients.

Developmental patterns of duration discrimination.

The purpose of this study was to determine whether the auditory perceptual abilities of children are characterized by an age-related improvement in duration discrimination. Forty children, ages 4 to 10 years, and 10 adults served as subjects. Difference limens were obtained using a 350-msec broadband noise burst as the standard stimulus in a three-interval forced-choice paradigm. Data were characterized by significant differences between the performances of the 4-, 6-, and 8-year-olds and those of the adults. Acquisition of adult-like discrimination performance was demonstrated between the ages of 8 and 10 years.

Coping With Communication Breakdown: A Program of Strategy Development for Children Who Have Hearing Losses.

Eight years of experience with the Communication Strategies Program have provided evidence that participation in a program of this type can lead to marked improvement in children's abilities to cope with communication breakdown. However, it is clear that children can not be expected to master every aspect of the program in 6 weeks. Most move through the program, learning the basic components during one summer, and then return in subsequent summers to expand their understanding of these concepts and/or to refine their application of the techniques they have been taught. Many children need work on specific vocabulary or syntax skills before they can tackle some of the issues related to causes of communication breakdown (e.g., unclear pronoun referents) or feelings encountered when communication breakdown occurs (e.g., frustration, confusion).This description of the program has focused on communication between a child who signs and children and adults who do not. However, the children were taught to use the same approach with individuals who do sign or can understand their speech. Marked improvement was seen in interactions among the children, between the children and the clinicians, and between the children and the dorm staff. Parent reports also indicate that benefits cut across many types of interactions. One mother told a local reporter that, "Jaclyn learned that there was a way to make herself understood- whether by sign, gestures, drawing, mimicking or pointing-and not to let anyone tell her anything different... . After the first summer in the University program, Jaclyn was much more sure of herself. She was willing to tackle anything" (Brown, 1989, p. 3).This program can be readily adapted to a variety of clinical and educational settings. The basic format can be varied to meet the needs of children of different ages, or with different degrees of hearing loss, cognitive abilities, or speech and language skills. The program can also be adjusted to fit within the time frame of school or clinic calendars.Within the SRP setting, the program has served as the foundation for discussing behavior in emergency situations, use of TDDs, and foreign languages. Formal descriptions of these aspects of the project are under development. It is likely that clinicians who experiment with the program will find additional ways to broaden the program's scope.

Thresholds of discomfort in young children.

Procedures for obtaining thresholds of discomfort from young children are almost nonexistent. This is likely due to the problems encountered in finding a task that they can easily perform. The purpose of this project was to design and test a procedure appropriate to the cognitive and language abilities of 4- to 5-yr-old hearing-impaired children. Data obtained from normally hearing subjects indicate that the procedure can be used with children whose mental ages are at or above 5 yr.

The effects of visual barriers used during auditory training on sound transmission.

Clinicians often use barriers such as paper or cardboard to eliminate visual cues during auditory training activities. Comparison of three commonly used barriers revealed substantial differences in the transmission of acoustic signals. A screen made of speaker mesh, the most acoustically transparent of the barriers tested, was judged to be the best option available.

Status of school children's hearing aids relative to monitoring practices.

Data concerning hearing aid monitoring practices and hearing aid malfunction were collected for three groups of mainstreamed hearing-impaired children: 248 children receiving services from itinerant teachers of the hearing impaired, 43 who participated in a study involving extensive psychoeducational evaluation, and 10 children who attended a 6 week residential treatment program in which hearing aid function was checked at least twice each day. Comparisons of the three data sets revealed that even conscientious parental and professional monitoring practices prove inadequate. As a result, it is hypothesized that children must take active roles in the monitoring process. A program to help children develop hearing aid monitoring skills is outlined.

Verbal communication skills of six children wit craniofacial anomalies.

The verbal communication skills of six children with craniofacial syndromes were examined. The subjects were four girls with Apert syndrome, a boy with Crouzon disease, and a fifth girl with Saethre-Chotzen Syndrome. They ranged in age from six to sixteen years. Each of the six subjects demonstrated oral structural anomalies and at least a mild communication problem. Sample size precluded the formation of judgments relative to the population as a whole or to particular subgroups.