Biomedical subjects

E M De Leenheer

Publications and source records attributed to E M De Leenheer.

4 recordsLinked to original sources

PubMed2001

Autosomal dominant inherited hearing impairment caused by a missense mutation in COL11A2 (DFNA13).

OBJECTIVE: To analyze the phenotype in a 5-generation DFNA13 family with a missense mutation in the COL11A2 gene that causes autosomal dominant, presumably prelingual, nonsyndromic sensorineural hearing impairment. DESIGN: Family study. SETTING: University hospital department. PATIENTS: Twenty mutation carriers from a large American kindred. METHODS: Cross-sectional analysis using pure-tone threshold measurements at 0.25, 0.5, 1, 2, 4, and 8 kHz. The audiometric configuration was evaluated according to an existing consensus protocol. The significance of features relating to audiometric configuration was tested using 1-way analysis of variance. Progression was evaluated with linear regression analyses of threshold-on-age. RESULTS: Most individuals showed midfrequency (U-shaped) characteristics. The mean threshold in generations IV and V was 44 dB at 1, 2, and 4 kHz (midfrequencies); it was 29 dB at the other frequencies (0.25, 0.5, and 8 kHz). There was no significant progression beyond presbyacusis. CONCLUSION: The trait in this family can be characterized as autosomal dominant, nonprogressive, presumably prelingual, midfrequency sensorineural hearing impairment.

Adolescent↗

PubMed2001

Speech recognition scores related to age and degree of hearing impairment in DFNA2/KCNQ4 and DFNA9/COCH.

OBJECTIVE: To analyze the relationship between pure-tone hearing threshold and speech recognition performance in DFNA2/KCNQ4 and DFNA9/COCH, 2 types of high-frequency nonsyndromic hearing impairment. DESIGN: Case series with cross-sectional analysis of phoneme recognition scores related to age and hearing level. SETTING: University hospital. PATIENTS: Forty-five members of 4 separate families, all carrying 1 of 3 different mutations in the KCNQ4 gene at the DFNA2 locus (1p34); 42 members of 7 separate families, all carrying the same Pro51Ser mutation in the COCH gene at the DFNA9 locus (14q12-q13). RESULTS: The deterioration of speech recognition dropped to a 90% score at a higher level of hearing impairment (pure-tone-average at 1, 2, and 4 kHz) in DFNA2-affected patients (65 dB) than in DFNA9-affected patients (46 dB). CONCLUSION: At similar levels of hearing impairment, DFNA2/KCNQ4-affected patients showed better speech recognition performance than DFNA9/COCH-affected patients.

Adult↗

PubMed2001

Novel coding-region polymorphisms in mitochondrial seryl-tRNA synthetase (SARSM) and mitoribosomal protein S12 (RPMS12) genes in DFNA4 autosomal dominant deafness families.

Two genes for components of the mitochondrial translational apparatus, mitochondrial seryl-tRNA synthetase (SARSM) and mitoribosomal protein S12 (RPMS12) lie adjacent to one another on human chromosome 19, within the critical interval for the autosomal dominant deafness locus DFNA4. Both genes are plausible candidates for DFNA4, based on the fact that deafness mutations in mtDNA have been mapped both to tRNA-ser(UCN) and to the accuracy domain of the small subunit rRNA. We have sequenced the coding regions, proximal promoters, 5' and 3' UTR and splice junctional regions of both genes in two families with DFNA4-linked deafness and in controls. Novel polymorphisms 84425C>T, 83907A>G, 79485T>G, 79406C>T, 71755A>C and 68686C>G (numbered as in GenBank AC011455) were found in one or both families, but none is a plausible disease-causing mutation. Although regulatory mutations affecting either gene could still be involved in the phenotype, structural gene mutations affecting SARSM or RPMS12 can be excluded from consideration as the cause of DFNA4-linked deafness, at least in the families identified thus far.

Chromosomes, Human, Pair 19↗

PubMed2001

The DFNA10 phenotype.

We present a detailed analysis of the DFNA10 phenotype based on data from 25 hearing-impaired persons coming from a large American pedigree segregating for deafness at the DFNA10 locus (chromosome 6q22.3-23.2). Cross-sectional analysis of air conduction threshold-on-age data from all available last-visit audiograms (linear regression analysis, age over 15 years) showed progression of hearing loss at a rate of 0.6 dB/y over all frequencies, with a flat to gently sloping age-corrected threshold of about 50 dB. The results were significant at 0.25, 4, and 8 kHz, but only if corrections for presbycusis were not included. Longitudinal threshold analysis performed in 1 case, covering ages 6 to 32 years, showed progression of hearing loss at a rate of 2 to 3 dB/y over 0.25 to 8 kHz. Nonlinear regression analysis was performed on phoneme discrimination scores with use of sigmoidal dose-response curves with variable slope. On the basis of these data, the hearing loss phenotype in this American DFNA10 family can be described as postlingual, initially progressive, and resulting, without the influence of presbycusis, in largely stable, flat sensorineural deafness.

Adolescent↗