Journal article
A NOVEL DFNB1 DELETION ALLELE SUPPORTS THE EXISTENCE OF A DISTANT CIS-REGULATORY REGION THAT CONTROLS GJB2 AND GJB6 EXPRESSION
Clinical genetics, Vol.78(3), pp.267-274
09/2010
DOI: 10.1111/j.1399-0004.2010.01387.x
PMCID: PMC2919588
PMID: 20236118
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 (arrayCGH), 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
, nor have we 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.
Details
- Title: Subtitle
- A NOVEL DFNB1 DELETION ALLELE SUPPORTS THE EXISTENCE OF A DISTANT CIS-REGULATORY REGION THAT CONTROLS GJB2 AND GJB6 EXPRESSION
- Creators
- Ellen Wilch - Genetics Program, Michigan State University, East Lansing MI 49224 USAHela Azaiez - Molecular Otolaryngology Research Laboratories, University of Iowa, Iowa City, IA 52242 USARachel A Fisher - Department of Pediatrics, Michigan State University, East Lansing, MI 48824 USAJill Elfenbein - Department of Communicative Sciences and Disorders, Michigan State University, East Lansing, MI 48824 USAAlessandra Murgia - Department of Pediatrics, University of Padua, 35128 Padua, ItalyRalf Birkenhäger - Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University Medical Center Freiburg, D-79106 Freiburg, GermanyHanno Bolz - Institute of Human Genetics, University of Cologne, Cologne 50931, GermanySueli Matilde Silva Costa - Centro de Biologia Molecular e Engenharia Genética (CBMEG), Universidade Estadual de Campinas (UNICAMP), Sao Paolo, BrazilIgnacio del Castillo - 1 Unidad de Genética Molecular, Hospital Universitario Ramón y Cajal, Madrid, Spain 2 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, SpainThomas Haaf - Institute of Human Genetics, Johannes Gutenberg University Mainz, 55131 Mainz, GermanyLies Hoefsloot - Nijmegen Centre of Molecular Life Sciences, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, 6500 HB Nijmegen, The NetherlandsHannie Kremer - Dept. Otorhinolaryngology, Radboud University Nijmegen Medical Centre, & Nijmegen Centre of Molecular Life Sciences, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, 6500 HB Nijmegen, The NetherlandsChristian Kubisch - Institute of Human Genetics, Center for Molecular Medicine Cologne, University of Cologne, Cologne 50931, GermanyCedric Le Marechal - Université Européenne de Bretagne & Université de Brest ; INSERM U613 ; Centre Hospitalier Universitaire (CHU) de Brest, Brest, FranceArti Pandya - Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298-0033 USAEdi Lúcia Sartorato - Centro de Biologia Molecular e Engenharia Genética (CBMEG), Universidade Estadual de Campinas (UNICAMP), Sao Paolo, BrazilEberhard Schneider - Institute of Human Genetics, Johannes Gutenberg University Mainz, 55131 Mainz, GermanyGuy Van Camp - Department of Medical Genetics, University and University Hospital of Antwerp, Antwerp, BelgiumWim Wuyts - Department of Medical Genetics, University and University Hospital of Antwerp, Antwerp, BelgiumRichard HJ Smith - Molecular Otolaryngology Research Laboratories and Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA 52242 USAKaren H Friderici - Department of Microbiology and Molecular Genetics and Department of Pediatrics, Michigan State University, East Lansing, MI 48824 USA
- Resource Type
- Journal article
- Publication Details
- Clinical genetics, Vol.78(3), pp.267-274
- DOI
- 10.1111/j.1399-0004.2010.01387.x
- PMID
- 20236118
- PMCID
- PMC2919588
- NLM abbreviation
- Clin Genet
- ISSN
- 0009-9163
- eISSN
- 1399-0004
- Language
- English
- Date published
- 09/2010
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984006313502771
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