A new large deletion in the DFNB1 locus causes nonsyndromic hearing loss.
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.
Feldmann
Delphine
D
Laboratoire de Biochimie, INSERM, U587, Centre de Référence des Surdités Génétiques, AP-HP, Hôpital Armand-Trousseau, 26 Avenue du Docteur-Arnold-Netter, 75012 Paris, France. delphine.feldmann@trs.aphp.fr
Le Maréchal
Cédric
C
Jonard
Laurence
L
Thierry
Patrick
P
Czajka
Cécile
C
Couderc
Remy
R
Ferec
Claude
C
Denoyelle
Françoise
F
Marlin
Sandrine
S
Fellmann
Florence
F
D000483:Alleles; D019943:Amino Acid Substitution; D001301:Audiometry, Pure-Tone; D001483:Base Sequence; D002675:Child, Preschool; D002882:Chromosomes, Human, Pair 13; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005819:Genetic Markers; D006239:Haplotypes; D034381:Hearing Loss / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008715:Methionine / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020161:Physical Chromosome Mapping; D017384:Sequence Deletion
D017630:Connexins; C000607042:GJB2 protein, human; D005819:Genetic Markers; D000072259:Connexin 26; D008715:Methionine