A seventh locus for otosclerosis, OTSC7, maps to chromosome 6q13–16.1

Thys, Melissa; Bogaert, Kris Van Den; Iliadou, Vasiliki Vivian; Vanderstraeten, Kathleen; Dieltjens, Nele; Schrauwen, Isabelle; Chen, Wenjie; Eleftheriades, Nikolaos; Grigoriadou, Maria; Pauw, Robert Jan; Cremers, Cor R W J; Smith, Richard J.H.; Petersen, Michael B.; Camp, Guy Van

doi:10.1038/sj.ejhg.5201761

Cited by 51 publications

(46 citation statements)

References 14 publications

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“…Genome-wide linkage analysis revealed a new locus, designated OTSC7, on chromosome 6q13-q16.1 [Thys et al, 2007]. In the present, Dutch family with six otosclerosis patients, suggestive linkage to the same region was found.…”

Section: Introductionsupporting

confidence: 54%

Phenotype description of a Dutch otosclerosis family with suggestive linkage to OTSC7

Pauw

Huygen

Thys

et al. 2007

American J of Med Genetics Pt A

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This study reports on a clinical investigation of a Dutch family that shows suggestive linkage to OTSC7. Cross-sectional as well as longitudinal analyses of audiometric data were performed. Also, high-resolution computed tomography (CT) images of the temporal bones from genetically affected family members were obtained to study the incidence and extent of otospongiotic foci. Audiometric data showed a considerable degree of phenotypic variability. Cross-sectional regression analysis did not show age-dependent progression of bone conduction (BC), air conduction (AC), and air-bone gap (ABG) levels. Longitudinal analysis of audiometric follow-up data of one family member showed age-dependent progression of AC, BC, and ABG levels. High-resolution CT images revealed an otospongiotic focus in six of six (100%) clinically affected individuals that carried the disease haplotype. In none of the clinically unaffected family members that showed linkage to OTSC7, an otospongiotic focus was detected by CT. In conclusion, hearing impairment in the present otosclerosis family seems to be variable in terms of onset age and level of progression. Long-term audiometric data of one patient proved to be valuable in understanding progression of hearing impairment in this individual. The detection rate of otospongiotic foci in our study group is similar compared to previous reports on CT data in consecutive otosclerosis patients who had stapes replacing surgery.

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Section: Introductionsupporting

confidence: 54%

Phenotype description of a Dutch otosclerosis family with suggestive linkage to OTSC7

Pauw

Huygen

Thys

et al. 2007

American J of Med Genetics Pt A

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“…Usually, OTSC transmits in an autosomal dominant fashion with reduced penetrance. In recent years, many efforts have been made to elucidate the molecular genetics of OTSC in multicase families, resulting in the identification of ten monogenic loci (Tomek et al, 1998;Van Den Bogaert et al, 2001;Chen et al, 2002;Van Den Bogaert et al, 2004;Brownstein et al, 2006;Thys et al, 2007b;Bel Hadj Ali et al, 2008;Weegerink et al, 2011). Despite meticulous searches through these regions, the disease causing genes have not been identified so far.…”

Section: Introductionmentioning

confidence: 99%

Genetic Association and Altered Gene Expression of Osteoprotegerin in Otosclerosis Patients

Priyadarshi

Ray

Biswal

et al. 2015

Annals of Human Genetics

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SummaryOtosclerosis (OTSC) is a late-onset hearing disorder characterized by increased bone turnover in the otic capsule. Disturbed osteoprotegerin expression has been found in the otosclerotic foci which may have an important role in the pathogenesis of OTSC. To identify the genetic risk factors, we sequenced the coding region and exon-intron boundaries of the OPG gene in 254 OTSC patients and 262 controls. Sequence analysis identified five known polymorphisms c.9C>G, c.30+15C>T, c.400+4C>T, c.768A>G, and c.817+8A>C. Testing of these SNPs revealed sex specific association with c.9C>G in males and c.30+15C>T in females after multiple correction. Furthermore, meta-analysis provided evidence of association of the c.9C>G polymorphism with OTSC. In secondary analysis, we investigated the mRNA expression of OPG and associated genes RANK and RANKL in otosclerotic tissues compared to controls. Expression analysis revealed significantly missing/reduced OPG expression only in otosclerotic tissues. However, the signal sequence polymorphism c.9C>G has shown no effect on OPG mRNA expression. In conclusion, our results suggest that the risk of OTSC is influenced by variations in the OPG gene along with other factors which might regulate its altered expression in otosclerotic tissues. Further research is warranted to elucidate the mechanisms underlying these observations.

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“…Linkage analysis studies on large families in which autosomal dominant otosclerosis segregates have been used to identify eight monogenic loci (OTSC1 (Tomek et al, 1998), OTSC2 (Van Den Bogaert et al, 2001), OTSC3 (Chen et al, 2002), OTSC4 (Brownstein et al, 2006), OTSC5 (Van Den Bogaert et al, 2004), OTSC7 (Thys et al, 2007b) and OTSC8 (Bel Hadj Ali et al, 2008)) located on chromosomes 15q25-q26, 7q34-36, 6p21.3-22.3, 16q21-23.2, 3q22-24, 6q13-16.1 and 9p13.1-9q21.11 respectively. The OTSC6 locus has not been published, although it has been reserved with the Human Genome Organisation Nomenclature Committee (http://www.genenames.org/).…”

Section: Introductionmentioning

confidence: 99%

Genetic variants in RELN are associated with otosclerosis in a non‐European population from Tunisia

Khalfallah¹,

Schrauwen

Mnaja

et al. 2010

Annals of Human Genetics

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SummaryOtosclerosis is a common form of conductive hearing loss, caused by an abnormal bone remodelling in the otic capsule. Both environmental and genetic factors have been implicated in the etiology of this disease. A recent genome wide association study identified two regions associated with otosclerosis, one on chr7q22.1, located in the RELN gene, and one on chr11q13.1. A second study in four European populations has replicated the association of the RELN gene with otosclerosis. To investigate the association of these loci with otosclerosis in a non-European population, we tested 11 SNPs from the two regions in 149 unrelated Tunisian patients and 152 controls. Four SNPs were significantly associated with otosclerosis. Three SNPs are located in the RELN region and the last one is located in the region on chromosome 11. We also observed a significant interaction with gender for rs3914132. This suggests an influence of sex on the association of RELN with otosclerosis. A meta-analysis showed that the disease-associated alleles in the Tunisian sample are the same as in all previously reported associations. Our study provides additional evidence implicating RELN in the development of otosclerosis. Additional functional studies should determine the role of RELN in the physiopathology of this disease.

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A seventh locus for otosclerosis, OTSC7, maps to chromosome 6q13–16.1

Cited by 51 publications

References 14 publications

Phenotype description of a Dutch otosclerosis family with suggestive linkage to OTSC7

Phenotype description of a Dutch otosclerosis family with suggestive linkage to OTSC7

Genetic Association and Altered Gene Expression of Osteoprotegerin in Otosclerosis Patients

Genetic variants in RELN are associated with otosclerosis in a non‐European population from Tunisia

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