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Steven J H Bom

Publications and source records attributed to Steven J H Bom.

7 recordsLinked to original sources
PubMed2005

Vestibular deterioration precedes hearing deterioration in the P51S COCH mutation (DFNA9): an analysis in 74 mutation carriers.

OBJECTIVES: To analyze cochleovestibular impairment features in P51S COCH mutation carriers (n = 22) in a new, large Dutch family and to compare the results to those obtained in previously identified similar mutation carriers (n = 52). To evaluate age-related features between progressive hearing and vestibular impairment of all mutation carriers (n = 74). STUDY DESIGN: Family study. METHODS: Regression analysis was performed in relation to age to outline the development of hearing thresholds, speech recognition scores, and vestibulo-ocular reflex time constant as the key vestibular response parameter. RESULTS: Pure tone thresholds, phoneme recognition scores, and vestibular responses of the mutation carriers in the new family were essentially similar to those previously established in all other mutation carriers. Hearing started to deteriorate in all mutation carriers from 43 years of age onwards, whereas deterioration of vestibular function started from age 34. CONCLUSION: Vestibular impairment starts earlier, progresses more rapidly, and, eventually, is more complete than hearing impairment in P51S COCH mutation carriers.

Adult↗
PubMed2003

Progression of low-frequency sensorineural hearing loss (DFNA6/14-WFS1).

OBJECTIVE: To assess the audiometric profile and speech recognition characteristics in affected members of 2 families with DFNA6/14 harboring heterozygous mutations in the WFS1 gene that cause an autosomal dominant nonsyndromic sensorineural hearing impairment trait. DESIGN: Family study. SETTING: Tertiary referral center. Patients Thirteen patients from 2 recently identified Dutch families with DFNA6/14 (Dutch III and IV). METHODS: Cross-sectional and longitudinal analyses of pure-tone thresholds at octave frequencies of 0.25 to 8 kHz were performed, and speech phoneme recognition scores were assessed. Progression was evaluated by linear regression analysis with and without correction for presbycusis. RESULTS: All individuals showed low-frequency hearing impairment. The 2-kHz frequency was more affected in the Dutch III family than in the Dutch IV family. Progressive hearing loss beyond presbycusis was found in the Dutch IV family and in 3 individuals in the Dutch III family. Annual threshold deterioration was between 0.6 and 1 dB per year at all frequencies. The speech recognition scores in the Dutch III family showed significantly more deterioration at increasing levels of hearing impairment compared with those in the Dutch IV family. CONCLUSION: Both families showed an autosomal dominant, progressive, low-frequency sensorineural hearing impairment caused by heterozygous WFS1 mutations.

Adolescent↗
PubMed2003

Cross-sectional analysis of hearing threshold in relation to age in a large family with cochleovestibular impairment thoroughly genotyped for DFNA9/COCH.

Hearing threshold was analyzed for each frequency in relation to age in 88 members of a large Dutch family with cochleovestibular impairment caused by a P51S mutation in the COCH gene within the DFNA9 locus (chromosome 14q12-13). The participants in this study were 34 mutation carriers and 54 relatives without the mutation (control subjects). A sigmoidal dose-response curve with a variable slope was used to fit the mutation carriers' threshold-on-age data. Progression started at about 40 years of age and only lasted for some 20 to 25 years; the associated average progression was 2.9 dB/y for all frequencies. However, some hearing impairment was already present before, predominantly at the high frequencies. The mean thresholds in the young mutation carriers (< 33 years of age) were significantly higher (by 4 to 13 dB) than those in age-matched controls at 2 to 8 kHz. Presumably, mutation carriers have a congenital, stable offset threshold (10 to 29 dB) at these frequencies, and develop progression later in life.

Adult↗
PubMed2002

Mutations in the WFS1 gene that cause low-frequency sensorineural hearing loss are small non-inactivating mutations.

Hereditary hearing impairment is an extremely heterogeneous trait, with more than 70 identified loci. Only two of these loci are associated with an auditory phenotype that predominantly affects the low frequencies (DFNA1 and DFNA6/14). In this study, we have completed mutation screening of the WFS1 gene in eight autosomal dominant families and twelve sporadic cases in which affected persons have low-frequency sensorineural hearing impairment (LFSNHI). Mutations in this gene are known to be responsible for Wolfram syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), which is an autosomal recessive trait. We have identified seven missense mutations and a single amino acid deletion affecting conserved amino acids in six families and one sporadic case, indicating that mutations in WFS1 are a major cause of inherited but not sporadic low-frequency hearing impairment. Among the ten WFS1 mutations reported in LFSNHI, none is expected to lead to premature protein truncation, and nine cluster in the C-terminal protein domain. In contrast, 64% of the Wolfram syndrome mutations are inactivating. Our results indicate that only non-inactivating mutations in WFS1 are responsible for non-syndromic low-frequency hearing impairment.

Audiometry↗
PubMed2002

Autosomal dominant low-frequency hearing impairment (DFNA6/14): a clinical and genetic family study.

OBJECTIVE: To delineate the phenotype and genotype of an autosomal dominant low-frequency sensorineural nonsyndromic hearing impairment trait in relation to similar traits. STUDY DESIGN: Family study, including retrospective case reviews. SETTING: Tertiary referral center. PATIENTS: Hearing impairment was documented in 11 family members in five generations, 8 of whom were alive and participated in this study. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Clinical study: medical and otologic history and examination, retrieval of previous audiograms, pure-tone audiometry, and statistical analysis of audiometric data. Genetic study: linkage analysis of blood samples in 18 clinically affected and nonaffected family members. RESULTS: Hearing impairment had been present since early childhood, mainly affecting the low frequencies (mean threshold 45 dB HL at 0.25-1 kHz); speech recognition was hardly affected during the first three decades of life. Higher frequencies became involved with increasing age, thus causing a flat-type audiogram at middle age and down-sloping audiograms after age 60 years. Progression was mild but significant at all frequencies (0.5 dB/year at 0.25 kHz to 1.3 dB/year at 8 kHz) and persisted after correction was applied for normal presbyacusis. The trait was linked to chromosome 4p16.3, in a region comprising both the previously located, closely adjacent DFNA6 and the DFNA14 loci for low-frequency hearing impairment. CONCLUSION: A third family (designated Dutch II) was identified with a low-frequency hearing impairment trait showing linkage to chromosome 4p16.3 (DFNA6/14). The progression of hearing impairment beyond presbyacusis in the current study is unprecedented for DFNA6/14 traits.

Adolescent↗