title: DFNB35 due to a novel mutation in the ESRRB gene in a Czech consanguineous family.
abstract: OBJECTIVE
  Non-syndromic hearing loss (NSHL) is a genetically heterogeneous disorder with mostly autosomal recessive inheritance. So far 40 genes and the same amount of loci with as yet unknown genes were described with autosomal recessive NSHL.
  
  
  METHODS
  A consanguineous Czech family with a child with NSHL was genotyped using SNP array and homozygous regions were compared with previously reported DFNB loci.
  
  
  RESULTS
  GRXCR1 and ESRRB genes associated with autosomal recessive NSHL were located in two of the eight homozygous regions detected by SNP array genotyping. Mutation p.R291L in a homozygous state was found in the deaf child, the parents were heterozygous. The entire coding region of the ESRRB gene was sequenced in additional 39 patients of Czech origin with early NSHL and only two variants, p.V413I and p.P386S, were found in homozygous state, but are considered to be polymorphisms.
  
  
  CONCLUSIONS
  Homozygosity mapping is a powerful method for identification of genes in heterogeneous recessive diseases. This is the first report of DFNB35 mutations in the Czech Republic and it seems to be a rare cause of NSHL. Additional mutations in ESRRB gene were reported in Pakistan, Tunisia and Turkey.
authors.affiliation: DNA laboratory, Department of Child Neurology, Charles University, 2nd Medical School and University Hospital Motol, Prague, Czech Republic. dana.brozkova@seznam.cz
authors.forename: Dana
authors.initials: D
authors.lastname: Šafka Brožková
authors.forename: Jana
authors.initials: J
authors.lastname: Laštůvková
authors.forename: Eliška
authors.initials: E
authors.lastname: Machalová
authors.forename: Jana
authors.initials: J
authors.lastname: Lisoňová
authors.forename: Marie
authors.initials: M
authors.lastname: Trková
authors.forename: Pavel
authors.initials: P
authors.lastname: Seeman
mesh_terms: D003241:Consanguinity; D018153:Czech Republic; D003638:Deafness / Q000235:genetics*; D005091:Exons; D006580:Genetic Carrier Screening; D005838:Genotype; D054477:Glutaredoxins / Q000235:genetics; D006720:Homozygote; D006801:Humans; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000235:genetics*
chemical_list: C490918:ESRRB protein, human; C547810:GRXCR1 protein, human; D054477:Glutaredoxins; D011960:Receptors, Estrogen