title: A novel DFNB31 mutation associated with Usher type 2 syndrome showing variable degrees of auditory loss in a consanguineous Portuguese family.
abstract: OBJECTIVE
  To identify the genetic defect of a consanguineous Portuguese family with rod-cone dystrophy and varying degrees of decreased audition.
  
  
  METHODS
  A detailed ophthalmic and auditory examination was performed on a Portuguese patient with severe autosomal recessive rod-cone dystrophy. Known genetic defects were excluded by performing autosomal recessive retinitis pigmentosa (arRP) genotyping microarray analysis and by Sanger sequencing of the coding exons and flanking intronic regions of eyes shut homolog-drosophila (EYS) and chromosome 2 open reading frame 71 (C2orf71). Subsequently, genome-wide homozygosity mapping was performed in DNA samples from available family members using a 700K single nucleotide polymorphism (SNP) microarray. Candidate genes present in the significantly large homozygous regions were screened for mutations using Sanger sequencing.
  
  
  RESULTS
  The largest homozygous region (~11 Mb) in the affected family members was mapped to chromosome 9, which harbors deafness, autosomal recessive 31 (DFNB31; a gene previously associated with Usher syndrome). Mutation analysis of DFNB31 in the index patient identified a novel one-base-pair deletion (c.737delC), which is predicted to lead to a truncated protein (p.Pro246HisfsX13) and co-segregated with the disease in the family. Ophthalmic examination of the index patient and the affected siblings showed severe rod-cone dystrophy. Pure tone audiometry revealed a moderate hearing loss in the index patient, whereas the affected siblings were reported with more profound and early onset hearing impairment.
  
  
  CONCLUSIONS
  We report a novel truncating mutation in DFNB31 associated with severe rod-cone dystrophy and varying degrees of hearing impairment in a consanguineous family of Portuguese origin. This is the second report of DFNB31 implication in Usher type 2.
authors: INSERM, U968, Paris, France. isabelle.audo@inserm.fr
authors: Isabelle
authors: I
authors: Audo
authors: Kinga
authors: K
authors: Bujakowska
authors: Saddek
authors: S
authors: Mohand-Saïd
authors: Sophie
authors: S
authors: Tronche
authors: Marie-Elise
authors: ME
authors: Lancelot
authors: Aline
authors: A
authors: Antonio
authors: Aurore
authors: A
authors: Germain
authors: Christine
authors: C
authors: Lonjou
authors: Wassila
authors: W
authors: Carpentier
authors: José-Alain
authors: JA
authors: Sahel
authors: Shomi
authors: S
authors: Bhattacharya
authors: Christina
authors: C
authors: Zeitz
mesh_terms: D000328:Adult; D017668:Age of Onset; D001483:Base Sequence; D002874:Chromosome Mapping; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D012720:Severity of Illness Index; D052245:Usher Syndromes / Q000235:genetics* / Q000473:pathology; D014787:Vision Tests
chemical_list: D008565:Membrane Proteins; C477219:WHRN protein, human