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001-es BibID:bibEBI00021206
Első szerző:Hilgert, Nele
Cím:Phenotypic variability of patients homozygous for the GJB2 mutation 35delG cannot be explained by the influence of one major modifier gene / Hilgert N., Huentelman M.J., Thorburn A.Q., Fransen E., Dieltjens N., Mueller-Malesinska M., Pollak A., Skorka A., Waligora J., Ploski R., Castorina P., Primignani P., Ambrosetti U., Murgia A., Orzan E., Pandya A., Arnos K., Norris V., Seeman P., Janousek P., Feldmann D., Marlin S., Denoyelle F., Nishimura C.J., Janecke A., Nekahm-Heis D., Martini A., Mennucci E., Tóth T., Sziklai I., Del Castillo I., Moreno F., Petersen M.B., Iliadou V., Tekin M., Incesulu A., Nowakowska E., Bal J., Van de Heyning P., Roux A. F., Blanchet C., Goizet C., Lancelot G., Fialho G., Caria H., Liu X.Z., Xiaomei O., Govaerts P., Gronskov K., Hostmark K., Frei K., Dhooge I., Vlaeminck S., Kunstmann E., Van Laer L., Smith R.J., Van Camp G.
Dátum:2009
Megjegyzések:Hereditary hearing loss (HL) is a very heterogeneous trait, with 46 gene identifications for non-syndromic HL. Mutations in GJB2 cause up to half of all cases of severe-to-profound congenital autosomal recessive non-syndromic HL, with 35delG being the most frequent mutation in Caucasians. Although a genotype-phenotype correlation has been established for most GJB2 genotypes, the HL of 35delG homozygous patients is mild to profound. We hypothesise that this phenotypic variability is at least partly caused by the influence of modifier genes. By performing a whole-genome association (WGA) study on 35delG homozygotes, we sought to identify modifier genes. The association study was performed by comparing the genotypes of mild/moderate cases and profound cases. The first analysis included a pooling-based WGA study of a first set of 255 samples by using both the Illumina 550K and Affymetrix 500K chips. This analysis resulted in a ranking of all analysed single-nucleotide polymorphisms (SNPs) according to their P-values. The top 250 most significantly associated SNPs were genotyped individually in the same sample set. All 192 SNPs that still had significant P-values were genotyped in a second independent set of 297 samples for replication. The significant P-values were replicated in nine SNPs, with combined P-values between 3 x 10(-3) and 1 x 10(-4). This study suggests that the phenotypic variability in 35delG homozygous patients cannot be explained by the effect of one major modifier gene. Significantly associated SNPs may reflect a small modifying effect on the phenotype. Increasing the power of the study will be of greatest importance to confirm these results.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
connexin 26
35delG
hereditary hearing loss
association study
modifier gene
Megjelenés:European Journal of Human Genetics. - 17 : 4 (2009), p. 517-524. -
További szerzők:Huentelman, Matthew J. Thorburn, Ashley Q. Fransen, Erik Dieltjens, Nele Mueller-Malesinska, Malgorzata Pollak, Agnieszka Skorka, Agata Waligora, Jaroslaw Ploski, Rafal Castorina, Pierangela Primignani, Paola Ambrosetti, Umberto Murgia, Alessandra Orzan, Eva Pandya, Arti Arnos, Kathleen Norris, Virginia Seeman, Pavel Janousek, Petr Feldmann, Delphine Marlin, Sandrine Denoyelle, Francoise Nishimura, Carla J. Janecke, Andreas Nekahm-Heis, Doris Martini, Alessandro Mennucci, Elena Tóth Tímea (1974-) (fül-orr-gégész) Sziklai István (1954-) (fül-orr-gégész) Del Castillo, Ignacio Moreno, Felipe Petersen, Michael B. Iliadou, Vasiliki Tekin, Mustafa Incesulu, Armagan Nowakowska, Ewa Bal, Jerzy Heyning, Paul, van de Roux, Anne-Francoise Blanchet, Catherine Goizet, Cyril Lancelot, Guenaelle Fialho, Graca Caria, Helena Liu, Xue Zhoung Xiaomei, Ouyang Govaerts, Paul Gronskov, Karen Hostmark, Karianne Frei, Klemens Dhooge, Ingeborg Vlaeminck, Stephen Kunstmann, Erdmute Laer, L., Van Smith, Richard J. Camp, Guy, Van
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2.

001-es BibID:BIBFORM040456
Első szerző:Snoeckx, Rikkert L
Cím:GJB2 Mutations and Degree of Hearing Loss : a Multicenter Study / Snoeckx R. L., Huygen P. L. M., Feldmann D., Marlin S., Denoyelle F., Waligora J., Mueller-Malesinska M., Pollak A., Ploski R., Murgia A., Orzan E., Castorina P., Ambrosetti U., Nowakowska-Szyrwinska E., Bal J., Wiszniewski W., Janecke A. R., Nekahm-Heis D., Seeman P., Bendova O., Kenna M. A., Frangulov A., Rehm H. L., Tekin M., Incesulu A., Dahl H. H. M., du Sart D., Jenkins L., Lucas D., Bitner-Glindzicz M., Avraham K. B., Brownstein Z., del Castillo I., Moreno F., Blin N., Pfister M., Sziklai I., Toth T., Kelley P. M., Cohn E. S., Van Maldergem L., Hilbert P., Roux A. F., Mondain M., Hoefsloot L. H., Cremers C. W., Löppönen T., Löppönen H., Parving A., Gronskov K., Schrijver I., Roberson J., Gualandi F., Martini A., Lina-Granade G., Pallares-Ruiz N., Correia C., Fialho G., Cryns K., Hilgert N., Van de Heyning P., Nishimura C. J., Smith R. J., Van Camp G.
Dátum:2005
ISSN:0002-9297
Megjegyzések:Hearing impairment (HI) affects 1 in 650 newborns, which makes it the most common congenital sensory impairment. Despite extraordinary genetic heterogeneity, mutations in one gene, GJB2, which encodes the connexin 26 protein and is involved in inner ear homeostasis, are found in up to 50% of patients with autosomal recessive nonsyndromic hearing loss. Because of the high frequency of GJB2 mutations, mutation analysis of this gene is widely available as a diagnostic test. In this study, we assessed the association between genotype and degree of hearing loss in persons with HI and biallelic GJB2 mutations. We performed cross-sectional analyses of GJB2 genotype and audiometric data from 1,531 persons, from 16 different countries, with autosomal recessive, mild-to-profound nonsyndromic HI. The median age of all participants was 8 years; 90% of persons were within the age range of 0-26 years. Of the 83 different mutations identified, 47 were classified as nontruncating, and 36 as truncating. A total of 153 different genotypes were found, of which 56 were homozygous truncating (T/T), 30 were homozygous nontruncating (NT/NT), and 67 were compound heterozygous truncating/nontruncating (T/NT). The degree of HI associated with biallelic truncating mutations was significantly more severe than the HI associated with biallelic nontruncating mutations (P<.0001). The HI of 48 different genotypes was less severe than that of 35delG homozygotes. Several common mutations (M34T, V37I, and L90P) were associated with mild-to-moderate HI (median 25-40 dB). Two genotypes--35delG/R143W (median 105 dB) and 35delG/dela(GJB6-D13S1830) (median 108 dB)--had significantly more-severe HI than that of 35delG homozygotes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:American Journal Of Human Genetics. - 77 : 6 (2005), p. 945-957. -
További szerzők:Huygen, Patrick L. M. Feldmann, Delphine Marlin, Sandrine Denoyelle, Francoise Waligora, Jaroslaw Mueller-Malesinska, Malgorzata Pollak, Agnieszka Ploski, Rafal Murgia, Alessandra Orzan, Eva Castorina, Pierangela Ambrosetti, Umberto Nowakowska-Szyrwinska, Ewa Bal, Jerzy Wiszniewski, Wojciech Janecke, Andreas Nekahm-Heis, Doris Seeman, Pavel Bendova, Olga Kenna, Margaret A. Frangulov, Anna Rehm, Heidi L. Tekin, Mustafa Incesulu, Armagan Dahl, Hans-Henrik M. du Sart, Desirée Jenkins, Lucy Lucas, Deirdre Bitner-Glindzicz, Maria Avraham, Karen B. Brownstein, Zippora Del Castillo, Ignacio Moreno, Felipe Blin, Nikolaus Pfister, Markus Sziklai István (1954-) (fül-orr-gégész) Tóth Tímea (1974-) (fül-orr-gégész) Kelley, Philip M. Cohn, Edward S. Van Maldergem, Lionel Hilbert, Pascale Roux, Anne-Francoise Mondain, Michel Hoefsloot, Lies H. Cremers, Cor W.R.J. Löppönen, Tuija Löppönen, Heikki Parving, Agnete Gronskov, Karen Schrijver, Iris Roberson, Joseph Gualandi, Francesca Martini, Alessandro Lina-Granade, Geneviéve Pallares-Ruiz, Nathalie Correia, Céu Fialho, Graca Cryns, Kim Hilgert, Nele Heyning, Paul, van de Nishimura, Carla J. Smith, Richard J. Camp, Guy, Van
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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