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Biomedical subjects

G Van Camp

Publications and source records attributed to G Van Camp.

At least 19 recordsLinked to original sources
PubMed2006

KCNQ4: a gene for age-related hearing impairment?

Age-related hearing impairment (ARHI) is the most common sensory impairment among the elderly. It is a complex disorder influenced by genetic as well as environmental factors. SNPs in a candidate susceptibility gene, KCNQ4, were examined in two independent Caucasian populations. Two quantitative trait locus (QTL) values were investigated: Zhigh and Zlow, a measure of high and respectively low frequency hearing loss. In the first population, the statistical analysis of 23 genotyped SNPs spread across KCNQ4 resulted in significant p-values for two SNPs for Zhigh-SNP9 (NT_004511:g.11244177A > T) and SNP15 (NT_004511:g.11257005C > T; NP_004691:p.Ala259Ala), and one SNP for Zlow-SNP12 (NT_004511:g.11249550A > T). The linkage disequilibrium (LD) structure of KCNQ4 was subsequently determined in a 34-kb region surrounding the significant SNPs, resulting in three LD-blocks. LD-block 1 contains SNP9 and covers an area of 5 kb, LD-block 2 measures 5 kb and surrounds SNP13 (NT_004511:g.11253513A > G) to SNP18 (NT_004511:g.11257509G > A; NP_004691:p.Thr293Thr), and LD-block 3 spans 7 kb. Five tag-SNPs of block 1 and 2, and 2 extra SNPs were subsequently genotyped in the second population. Again, several SNPs were positively associated with ARHI: one SNP (SNP18) for the high frequencies and three SNPs (SNP9, SNP12, and SNP18) for the low frequencies, although only a single SNP (SNP12) resulted in significant p-values in both populations. Nevertheless, the associated SNPs of both populations were all located in the same 13-kb region in the middle of the KCNQ4 gene.

Adult↗
PubMed2005

Abnormal response to inotropic stimulation in young asymptomatic type I diabetic patients demonstrated by serial gated myocardial perfusion SPECT imaging.

PURPOSE: In subjects without underlying cardiac disease dobutamine is known to enhance systolic LV function and LV relaxation. As end-systolic (ES) and end-diastolic (ED) volumes (V) can be derived from gated SPECT we intent to study these volumes and their response to dobutamine in order to have a better understanding of the mechanism by which stroke volume (SV) increases during dobutamine infusion. We intent to do this in normal controls and in young diabetic subjects. METHODS: After injection of sestamibi, serial gated SPECT were obtained at baseline, and during low doses of dobutamine infusion in 12 asymptomatic type I diabetic patients, and in 12 age matched controls. LV EDV, ESV, SV and EF were calculated with the QGS program. RESULTS: Gated SPECT showed comparable LV EF and SV in both groups at rest. There was a significant increase in LVEF and SV during dobutamine infusion but in the diabetic patients the increase in SV was due to a decrease in ESV from 25+/-5 to 20+/-6 ml/m2 (p=0.002) and no change in EDV. In normal controls, the increase in EF was due to an increase in EDV from 69+/-10 to 73+/-12 ml/m2 (p=0.002) with no significant change in ESV. CONCLUSION: These data confirm the presence of subclinical abnormalities of diastolic function in asymptomatic type I diabetic patients and show differences in adaptation to inotropic stimulation in order to preserve the increase in stroke volume and LV ejection fraction.

Adult↗
PubMed2005

Mutation of COL11A2 causes autosomal recessive non-syndromic hearing loss at the DFNB53 locus.

BACKGROUND: Allele variants of COL11A2, encoding collagen type XI alpha2, cause autosomal dominant non-syndromic hearing loss (ARNSHL) at the DFNA13 locus (MIM 601868) and various syndromes that include a deafness phenotype. OBJECTIVE: To describe a genome-wide scan carried out on a consanguineous Iranian family segregating ARNSHL. RESULTS: Genotyping data identified a novel locus for ARNSHL on chromosome 6p21.3, which was designated DFNB53. Homozygosity for the P621T mutation of COL11A2 was present in all deaf persons in this family; this same variation was absent in 269 Iranian controls. Sequence comparison of collagen type XI alpha1 and alpha2 peptides across species shows that the replaced proline is an evolutionarily conserved amino acid. CONCLUSIONS: The P621T mutation of COL11A2 affects the Y position of the canonical -Gly-X-Y- repeat in collagens. It lies near the amino-terminus of the triple helical region and causes ARNSHL. This finding suggests that mutation type and location are critical determinants in defining the phenotype of COL11A2 associated diseases.

Amino Acid Sequence↗
PubMed2005

Genetic testing for hearing impairment.

For some patients, genetic testing can reveal the etiology of their hearing impairment, and can provide evidence for a medical diagnosis. However, a gap between fundamental genetic research on hereditary deafness and clinical otology emerges because of the steadily increasing number of discovered genes for hereditary hearing impairment (HHI) and the comparably low clinical differentiation of the HHIs. In an attempt to keep up with the scientific progress, this article enumerates the indications of genetic testing for HHI from a clinical point of view and describes the most frequently encountered HHIs in Belgium. Domains of recent scientific interest, molecular biological aspects, and some pitfalls with HHIs are highlighted. The overview comprises bilateral congenital hearing loss, late-onset progressive high frequency hearing loss, progressive bilateral cochleo-vestibular deficit, and progressive low frequency hearing loss. Also, several syndromal forms of HHI are summarized, and the availability of genetic tests mentioned. Finally, the requirements for successful linkage analysis, an important genetic research tool for localizing the potential genes of a trait on a chromosome, are briefly described.

Belgium↗
PubMed2004

Contrast harmonic imaging improves the evaluation of left ventricular function in ventilated patients: comparison with transesophageal echocardiography.

AIMS: The study examined the value of contrast echocardiography (CE) in the assessment of left ventricular (LV) wall motion in ventilated patients in comparison with transesophageal (TOE) and standard fundamental transthoracic imaging (SE). METHODS: Transthoracic echocardiograms were done in 40 ventilated patients. Wall motion was evaluated using the recommendations of the American Society of Echocardiography on SE, CE and TOE. A visualization score was assigned on a scale of 2-0 for each of 16 segments. The segment was assigned a value of 2 if the segment was seen in both systole and diastole, 1 if seen only in systole or diastole, and 0 if not seen at all. A confidence score was also given for each segment with each technique (unable to evaluate; not sure; sure). The ejection fraction (EF) was estimated visually for each technique, and a confidence score was also applied to the EF. RESULTS: Visualization score 0 was present in 6.2 segments/patient on SE, 1.2 on CE (P<0.0001) and 1.1 on TOE (P<0.0001). An average of 6.5 segments were read with surety on SE, 11.5 on CE (P<0.0001) and 12.3 on TOE ( P<0.0001 ). There was no significant difference for CE vs TOE. EF was uninterpretable in 32% on SE, 0% on CE (P<0.001 and 0% on TOE (P<0.001). The EF was read with surety in 53% of patients on SE, 88% on CE (P < 0.0001) and 93% with TOE (P<0.0001) with no difference for CE vs TOE. Thus, wall motion was seen with more confidence on CE and TOE. CONCLUSIONS: In the ventilated patients with suboptimal transthoracic echocardiograms for the evaluation of the LV function, CE provides image quality of regional and global LV function similar to that achieved with TOE echocardiography.

Aged↗
PubMed2004

A novel locus for autosomal dominant non-syndromic hearing loss, DFNA31, maps to chromosome 6p21.3.

BACKGROUND: Non-syndromic hearing loss is the most genetically heterogeneous trait known in humans. To date, 51 loci for autosomal dominant non-syndromic sensorineural hearing loss (NSSHL) have been identified by linkage analysis. OBJECTIVE: To investigate the genes involved in a Dutch family with NSSHL. METHODS: Linkage analysis in a large Dutch pedigree with progressive bilateral loss of the mid and high frequencies, in which a novel dominant locus for postlingual NSSHL (DFNA31) has been identified. RESULTS: DFNA31 was found to be located in a 7.5 cM region of chromosome 6p21.3 between D6S276 (telomeric) and D6S273 (centromeric), with a maximum two point LOD score of 5.99 for D6S1624. DNA sequencing of coding regions and exon/intron boundaries of two candidate genes (POU5F1, GABBR1) in this interval did not reveal disease causing mutations. CONCLUSIONS: Haplotype analysis indicated that the genetic defect in this family does not overlap the DFNA13 and DFNA21 regions that are also located on 6p. Identification of the disease gene will be of major importance in understanding the pathophysiology of hearing impairment.

Age of Onset↗
PubMed2004

A genotype-phenotype correlation for GJB2 (connexin 26) deafness.

INTRODUCTION: Mutations in GJB2 are the most common cause of non-syndromic autosomal recessive hearing impairment, ranging from mild to profound. Mutation analysis of this gene is widely available as a genetic diagnostic test. OBJECTIVE: To assess a possible genotype-phenotype correlation for GJB2. DESIGN: Retrospective analysis of audiometric data from people with hearing impairment, segregating two GJB2 mutations. SUBJECTS: Two hundred and seventy seven unrelated patients with hearing impairment who were seen at the ENT departments of local and university hospitals from Italy, Belgium, Spain, and the United States, and who harboured bi-allelic GJB2 mutations. RESULTS: We found that 35delG homozygotes have significantly more hearing impairment, compared with 35delG/non-35delG compound heterozygotes. People with two non-35delG mutations have even less hearing impairment. We observed a similar gradient of hearing impairment when we categorised mutations as inactivating (that is, stop mutations or frame shifts) or non-inactivating (that is, missense mutations). We demonstrated that certain mutation combinations (including the combination of 35delG with the missense mutations L90P, V37I, or the splice-site mutation IVS1+1G>A, and the V37I/V37I genotype) are associated with significantly less hearing impairment compared with 35delG homozygous genotypes. CONCLUSIONS: This study is the first large systematic analysis indicating that the GJB2 genotype has a major impact on the degree of hearing impairment, and identifying mild genotypes. Furthermore, this study shows that it will be possible to refine this correlation and extend it to additional genotypes. These data will be useful in evaluating habilitation options for people with GJB2 related deafness.

Adolescent↗
PubMed2004

DFNA5: hearing impairment exon instead of hearing impairment gene?

BACKGROUND: Three mutations in the DFNA5 gene have been described in three families with autosomal dominant non-syndromic hearing impairment. Although these mutations are different at the genomic DNA level, they all lead to skipping of exon 8 at the mRNA level. We hypothesise that hearing impairment associated with DFNA5 is caused by a highly unusual mechanism, in which skipping of one specific exon leads to disease that is not caused by other mutations in this gene. We hypothesise that this represents a very specific "gain of function" mutation, with the truncated protein exerting a deleterious new function. METHODS: We performed transfection experiments in mammalian cell lines (HEK293T and COS-1) with green fluorescent protein (GFP) tagged wildtype and mutant DFNA5 and analysed cell death with flow cytometry and fluorescence microscopy. RESULTS: Post-transfection death of HEK293T cells approximately doubled when cells were transfected with mutant DFNA5-GFP compared with wildtype DFNA5-GFP. Cell death was attributed to necrotic events and not to apoptotic events. CONCLUSION: The transfection experiments in mammalian cell lines support our hypothesis that the hearing impairment associated with DFNA5 is caused by a "gain of function" mutation and that mutant DFNA5 has a deleterious new function.

Animals↗
PubMed2003

Heart valvular disease in patients with Parkinson's disease treated with high-dose pergolide.

The authors report the clinical, echocardiographic, and pathologic findings in two patients treated with more than 5 mg of pergolide daily who developed symptomatic severe heart failure due to restrictive valvular disease. They also describe the echocardiographic data of another eight patients taking similar doses of pergolide presenting no clinical signs of heart failure. The findings suggest a possible role of high doses of pergolide in inducing restrictive valvular disease.

Aged↗
PubMed2003

Metyrapone-induced glucocorticoid depletion modulates tyrosine hydroxylase and phenylethanolamine N-methyltransferase gene expression in the rat adrenal gland by a noncholinergic transsynaptic activation.

The hypothalamic corticotropin-releasing hormone system and the sympathetic nervous system are anatomically and functionally interconnected and hormones of the hypothalamic-pituitary-adrenocortical axis contribute to the regulation of catecholaminergic systems. To investigate the role of glucocorticoids on activity of the adrenal gland, we analysed plasma and adrenal catecholamines, tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) mRNA expression in rats injected with metyrapone or dexamethasone. Metyrapone-treated rats had significantly lower epinephrine and higher norepinephrine production than control rats. Metyrapone increased TH protein synthesis and TH mRNA expression whereas its administration did not affect PNMT mRNA expression. Dexamethasone restored plasma and adrenal epinephrine concentrations and increased PNMT mRNA levels, which is consistent with an absolute requirement of glucocorticoids for PNMT expression. Adrenal denervation completely abolished the metyrapone-induced TH mRNA expression. Blockage of cholinergic neurotransmission by nicotinic or muscarinic receptor antagonists did not prevent the metyrapone-induced rise in TH mRNA. Finally, pituitary adenylate cyclase activating polypeptide (PACAP) adrenal content was not affected by metyrapone. These results provide evidence that metyrapone-induced corticosterone depletion elicits transsynaptic TH activation, implying noncholinergic neurotransmission. This may involve neuropeptides other than PACAP.

Adrenal Glands↗
PubMed2003

Native valve endocarditis with aorta-to-left atrial fistula due to Corynebacterium amycolatum.

Infective endocarditis remains a pathology with a high rate of complications and mortality. One of the most dramatic complications is abscess formation. A rare evolution of abscess formation is the development of fistula. We describe an 88-year-old woman with an aortic root abscess and aorta-to-left atrial fistula. To our knowledge this has only been described with streptococcus species as causative micro-organism. In this case the abscess was caused by Corynebacterium amycolatum, which is an infrequently found micro-organism.

Abscess↗
PubMed2002

Otosclerosis: a genetically heterogeneous disease involving at least three different genes.

Otosclerosis is caused by abnormal bone homeostasis of the otic capsule, resulting in hearing impairment in 0.3%-0.4% of the white population. The etiology of the disease remains unclear and environmental as well as genetic factors have been implicated. We localized the first autosomal-dominant locus to chromosome 15 in 1998 (OTSC1) in an Indian family and, recently, we reported the localization of a second gene for otosclerosis to a 16 cM interval on chromosome 7q (OTSC2). In this study, we recruited and analyzed nine additional families (seven Belgian and two Dutch families with 53 affected and 20 unaffected subjects) to investigate the importance of these loci in autosomal-dominant otosclerosis. We completed linkage analysis with three microsatellite markers of chromosome 15 (D15S652, D15S1004, D15S657) and five microsatellite markers of chromosome 7 (D7S495, D7S2560, D7S684, D7S2513, D7S2426). In two families, results compatible with linkage to OTSC2 were found, but in the seven remaining families OTSC1 and OTSC2 were excluded. Heterogeneity testing provided significant evidence for genetic heterogeneity, with an estimated 25% of families linked to OTSC2. These results indicate that, besides OTSC1 and OTSC2, there must be at least one additional otosclerosis locus.

Chromosomes, Human, Pair 15↗
PubMed2002

Linkage of otosclerosis to a third locus (OTSC3) on human chromosome 6p21.3-22.3.

Clinical otosclerosis (OMIM 166800/605727) has a prevalence of 0.2-1% among white adults, making it the single most common cause of hearing impairment in this group. It is caused by abnormal bone homeostasis of the otic capsule with the consequent development of sclerotic foci that invade the stapedio-vestibular joint (oval window) interfering with free motion of the stapes. Impaired ossicular chain mobility results in a conductive hearing loss. We identified the first locus for otosclerosis (OTSC1) on chromosome 15 in 1998 and reported a second locus (OTSC2) on chromosome 7 last year. Here we present results of a genome wide linkage study on a large Cypriot family segregating otosclerosis. Results of this study exclude linkage to OTSC1 and OTSC2 and identify a third locus, OTSC3, on chromosome 6p. The defined OTSC3 interval covers the HLA region, consistent with reported associations between HLA-A/HLA-B antigens and otosclerosis.

Chromosome Mapping↗
PubMed2002

Interpretation of pure-tone thresholds in sensorineural hearing loss (SNHL): a review of measurement variability and age-specific references.

When assessing a patient with a sensorineural hearing impairment, the most simple and most widely available technical investigation is pure-tone audiometry. Although it is a subjective measure, the test is very reliable if the patient is cooperative. In this paper we review standards and test-retest reliability for pure-tone audiometry. A pure-tone threshold measurement at a single frequency has a chance of 90% to be repeated between -10 dB and +10 dB compared to the first measurement, assuming no real change in hearing thresholds has occurred. It is also of great importance to use correct gender- and age-specific reference values when interpreting pure-tone threshold measurements. Several large-scale epidemiological studies have been conducted during recent years, and have provided us with reliable gender- and age-specific references. A method to take into account the age-related deterioration is presented. In this method, Z-score audiograms represent traditional thresholds in an age- and gender-independent way. At each frequency, the Z-score value is the number of standard deviation units that the threshold differs from the median value for the otologically normal population (ISO 7029).

Adult↗