A New Large Deletion in the DFNB1 Locus Causes Nonsyndromic Hearing Loss.
Details
Serval ID
serval:BIB_3366BBBA01A5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A New Large Deletion in the DFNB1 Locus Causes Nonsyndromic Hearing Loss.
Journal
European Journal of Medical Genetics
ISSN
1878-0849[electronic]
Publication state
Published
Issued date
2009
Volume
52
Number
4
Pages
195-200
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Mutations in the GJB2 gene encoding the gap junction protein connexin 26 are responsible for up to 30% of all cases of autosomal recessive nonsyndromic hearing impairment (HI) with prelingual onset in most populations. The corresponding locus DFNB1, located on chromosome 13q11-q12, is also affected by three distinct deletions. These deletions extended distally to GJB2, which remains intact. We report a novel large deletion in DFNB1 observed in a patient presenting profound prelingual HI. This deletion was observed in trans to a GJB2 mutated allele carrying the p.Val84Met (V84M) mutation and was shown to be associated with hearing loss. The deletion caused a false homozygosity of V84M in the proband. Quantification of alleles by quantitative fluorescent multiplex PCR (QFM-PCR) enabled us to study the breakpoints of the deletion. The deleted segment extended through at least 920kb and removed the three connexin genes GJA3, GJB2 and GJB6. The distal breakpoint inside intron 2 of CRYL1 gene differed from the breakpoints of the known DFNB1 deletions. This case highlights the importance of screening for large deletions in molecular studies of GJB2.
Keywords
Alleles, Amino Acid Substitution, Audiometry, Pure-Tone, Base Sequence, Child, Preschool, Chromosomes, Human, Pair 13, Connexins/genetics, DNA Mutational Analysis, Genetic Markers, Haplotypes, Hearing Loss/genetics, Hearing Loss/physiopathology, Humans, Male, Methionine/metabolism, Molecular Sequence Data, Mutation, Pedigree, Physical Chromosome Mapping, Sequence Deletion
Pubmed
Web of science
Create date
09/02/2010 11:19
Last modification date
20/08/2019 13:19