A novel DFNB1 deletion allele supports the existence of a distant cis-regulatory region that controls GJB2 and GJB6 expression.

E Wilch; H Azaiez; R A Fisher; J Elfenbein; A Murgia; R Birkenhäger; H Bolz; S M Da Silva-Costa; I Del Castillo; T Haaf; L Hoefsloot; H Kremer; Christian Kubisch; C Le Marechal; A Pandya; E L Sartorato; E Schneider; G Van Camp; W Wuyts; R J H Smith; K H Friderici

A novel DFNB1 deletion allele supports the existence of a distant cis-regulatory region that controls GJB2 and GJB6 expression.

Standard

A novel DFNB1 deletion allele supports the existence of a distant cis-regulatory region that controls GJB2 and GJB6 expression. / Wilch, E; Azaiez, H; Fisher, R A; Elfenbein, J; Murgia, A; Birkenhäger, R; Bolz, H; Da Silva-Costa, S M; Del Castillo, I; Haaf, T; Hoefsloot, L; Kremer, H; Kubisch, Christian; Le Marechal, C; Pandya, A; Sartorato, E L; Schneider, E; Van Camp, G; Wuyts, W; Smith, R J H; Friderici, K H.

in: CLIN GENET, Jahrgang 78, Nr. 3, 3, 2010, S. 267-274.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Wilch, E, Azaiez, H, Fisher, RA, Elfenbein, J, Murgia, A, Birkenhäger, R, Bolz, H, Da Silva-Costa, SM, Del Castillo, I, Haaf, T, Hoefsloot, L, Kremer, H, Kubisch, C, Le Marechal, C, Pandya, A, Sartorato, EL, Schneider, E, Van Camp, G, Wuyts, W, Smith, RJH & Friderici, KH 2010, 'A novel DFNB1 deletion allele supports the existence of a distant cis-regulatory region that controls GJB2 and GJB6 expression.', CLIN GENET, Jg. 78, Nr. 3, 3, S. 267-274. <http://www.ncbi.nlm.nih.gov/pubmed/20236118?dopt=Citation>

APA

Wilch, E., Azaiez, H., Fisher, R. A., Elfenbein, J., Murgia, A., Birkenhäger, R., Bolz, H., Da Silva-Costa, S. M., Del Castillo, I., Haaf, T., Hoefsloot, L., Kremer, H., Kubisch, C., Le Marechal, C., Pandya, A., Sartorato, E. L., Schneider, E., Van Camp, G., Wuyts, W., ... Friderici, K. H. (2010). A novel DFNB1 deletion allele supports the existence of a distant cis-regulatory region that controls GJB2 and GJB6 expression. CLIN GENET, 78(3), 267-274. [3]. http://www.ncbi.nlm.nih.gov/pubmed/20236118?dopt=Citation

Vancouver

Wilch E, Azaiez H, Fisher RA, Elfenbein J, Murgia A, Birkenhäger R et al. A novel DFNB1 deletion allele supports the existence of a distant cis-regulatory region that controls GJB2 and GJB6 expression. CLIN GENET. 2010;78(3):267-274. 3.

Bibtex

@article{4349c49faf9e4c61af6d6f3911f88a6e,

title = "A novel DFNB1 deletion allele supports the existence of a distant cis-regulatory region that controls GJB2 and GJB6 expression.",

abstract = "Eleven affected members of a large German-American family segregating recessively inherited, congenital, non-syndromic sensorineural hearing loss (SNHL) were found to be homozygous for the common 35delG mutation of GJB2, the gene encoding the gap junction protein Connexin 26. Surprisingly, four additional family members with bilateral profound SNHL carried only a single 35delG mutation. Previously, we demonstrated reduced expression of both GJB2 and GJB6 mRNA from the allele carried in trans with that bearing the 35delG mutation in these four persons. Using array comparative genome hybridization (array CGH), we have now identified on this allele a deletion of 131.4 kb whose proximal breakpoint lies more than 100 kb upstream of the transcriptional start sites of GJB2 and GJB6. This deletion, del(chr13:19,837,344-19,968,698), segregates as a completely penetrant DFNB1 allele in this family. It is not present in 528 persons with SNHL and monoallelic mutation of GJB2 or GJB6, and we have not identified any other candidate pathogenic copy number variation by arrayCGH in a subset of 10 such persons. Characterization of distant GJB2/GJB6 cis-regulatory regions evidenced by this allele may be required to find the 'missing' DFNB1 mutations that are believed to exist.",

keywords = "Humans, Male, Female, Genotype, Molecular Sequence Data, Base Sequence, Comparative Genomic Hybridization, Pedigree, Family Health, Alleles, Genetic Testing, Chromosome Deletion, *Gene Expression Regulation, *Sequence Deletion, Sequence Homology, Nucleic Acid, Chromosomes, Human, Pair 13/genetics, Connexins/*genetics, Hearing Loss, Sensorineural/diagnosis/genetics, Penetrance, Regulatory Sequences, Nucleic Acid/*genetics, Humans, Male, Female, Genotype, Molecular Sequence Data, Base Sequence, Comparative Genomic Hybridization, Pedigree, Family Health, Alleles, Genetic Testing, Chromosome Deletion, *Gene Expression Regulation, *Sequence Deletion, Sequence Homology, Nucleic Acid, Chromosomes, Human, Pair 13/genetics, Connexins/*genetics, Hearing Loss, Sensorineural/diagnosis/genetics, Penetrance, Regulatory Sequences, Nucleic Acid/*genetics",

author = "E Wilch and H Azaiez and Fisher, {R A} and J Elfenbein and A Murgia and R Birkenh{\"a}ger and H Bolz and {Da Silva-Costa}, {S M} and {Del Castillo}, I and T Haaf and L Hoefsloot and H Kremer and Christian Kubisch and {Le Marechal}, C and A Pandya and Sartorato, {E L} and E Schneider and {Van Camp}, G and W Wuyts and Smith, {R J H} and Friderici, {K H}",

year = "2010",

language = "English",

volume = "78",

pages = "267--274",

journal = "CLIN GENET",

issn = "0009-9163",

publisher = "Wiley-Blackwell",

number = "3",

}

RIS

TY - JOUR

T1 - A novel DFNB1 deletion allele supports the existence of a distant cis-regulatory region that controls GJB2 and GJB6 expression.

AU - Wilch, E

AU - Azaiez, H

AU - Fisher, R A

AU - Elfenbein, J

AU - Murgia, A

AU - Birkenhäger, R

AU - Bolz, H

AU - Da Silva-Costa, S M

AU - Del Castillo, I

AU - Haaf, T

AU - Hoefsloot, L

AU - Kremer, H

AU - Kubisch, Christian

AU - Le Marechal, C

AU - Pandya, A

AU - Sartorato, E L

AU - Schneider, E

AU - Van Camp, G

AU - Wuyts, W

AU - Smith, R J H

AU - Friderici, K H

PY - 2010

Y1 - 2010

N2 - Eleven affected members of a large German-American family segregating recessively inherited, congenital, non-syndromic sensorineural hearing loss (SNHL) were found to be homozygous for the common 35delG mutation of GJB2, the gene encoding the gap junction protein Connexin 26. Surprisingly, four additional family members with bilateral profound SNHL carried only a single 35delG mutation. Previously, we demonstrated reduced expression of both GJB2 and GJB6 mRNA from the allele carried in trans with that bearing the 35delG mutation in these four persons. Using array comparative genome hybridization (array CGH), we have now identified on this allele a deletion of 131.4 kb whose proximal breakpoint lies more than 100 kb upstream of the transcriptional start sites of GJB2 and GJB6. This deletion, del(chr13:19,837,344-19,968,698), segregates as a completely penetrant DFNB1 allele in this family. It is not present in 528 persons with SNHL and monoallelic mutation of GJB2 or GJB6, and we have not identified any other candidate pathogenic copy number variation by arrayCGH in a subset of 10 such persons. Characterization of distant GJB2/GJB6 cis-regulatory regions evidenced by this allele may be required to find the 'missing' DFNB1 mutations that are believed to exist.

AB - Eleven affected members of a large German-American family segregating recessively inherited, congenital, non-syndromic sensorineural hearing loss (SNHL) were found to be homozygous for the common 35delG mutation of GJB2, the gene encoding the gap junction protein Connexin 26. Surprisingly, four additional family members with bilateral profound SNHL carried only a single 35delG mutation. Previously, we demonstrated reduced expression of both GJB2 and GJB6 mRNA from the allele carried in trans with that bearing the 35delG mutation in these four persons. Using array comparative genome hybridization (array CGH), we have now identified on this allele a deletion of 131.4 kb whose proximal breakpoint lies more than 100 kb upstream of the transcriptional start sites of GJB2 and GJB6. This deletion, del(chr13:19,837,344-19,968,698), segregates as a completely penetrant DFNB1 allele in this family. It is not present in 528 persons with SNHL and monoallelic mutation of GJB2 or GJB6, and we have not identified any other candidate pathogenic copy number variation by arrayCGH in a subset of 10 such persons. Characterization of distant GJB2/GJB6 cis-regulatory regions evidenced by this allele may be required to find the 'missing' DFNB1 mutations that are believed to exist.

KW - Humans

KW - Male

KW - Female

KW - Genotype

KW - Molecular Sequence Data

KW - Base Sequence

KW - Comparative Genomic Hybridization

KW - Pedigree

KW - Family Health

KW - Alleles

KW - Genetic Testing

KW - Chromosome Deletion

KW - Gene Expression Regulation

KW - Sequence Deletion

KW - Sequence Homology, Nucleic Acid

KW - Chromosomes, Human, Pair 13/genetics

KW - Connexins/genetics

KW - Hearing Loss, Sensorineural/diagnosis/genetics

KW - Penetrance

KW - Regulatory Sequences, Nucleic Acid/genetics

KW - Humans

KW - Male

KW - Female

KW - Genotype

KW - Molecular Sequence Data

KW - Base Sequence

KW - Comparative Genomic Hybridization

KW - Pedigree

KW - Family Health

KW - Alleles

KW - Genetic Testing

KW - Chromosome Deletion

KW - Gene Expression Regulation

KW - Sequence Deletion

KW - Sequence Homology, Nucleic Acid

KW - Chromosomes, Human, Pair 13/genetics

KW - Connexins/genetics

KW - Hearing Loss, Sensorineural/diagnosis/genetics

KW - Penetrance

KW - Regulatory Sequences, Nucleic Acid/genetics

M3 - SCORING: Journal article

VL - 78

SP - 267

EP - 274

JO - CLIN GENET

JF - CLIN GENET

SN - 0009-9163

IS - 3

M1 - 3

ER -