OBJECTIVES: To evaluate the contribution of eight small NSHL-AR (non-syndromic deafness, autosomal recessive) genes to hereditary hearing loss in Czech patients. PATIENTS AND METHODS: Unrelated Czech patients, adults and children, diagnosed with pre-lingual hereditary hearing loss with at least one similarly affected deaf sibling and with previously excluded mutations in the GJB2 gene were investigated by Sanger sequencing of the selected eight small NSHL-AR associated genes (CABP2 - 51 patients, CIB2 - 45 patients, PJVK/DFNB59 - 53 patients, GJB3 - 46 patients, ILDR1 - 48 patients, LHFPL5 - 66 patients, LRTOMT - 60 patients, TMIE - 64 patients). RESULTS: Mutations were detected in the LHFPL5 (DFNB67) gene. The patient is heterozygote for two already described pathogenic variants (p.Tyr127Cys, p.Thr165Met). In five samples, five rare heterozygous variants (two novel) predicted as pathogenic were detected in genes CABP2, ILDR1, LHFPL5 and LRTOMT. CONCLUSION: Mutations in eight small NSHL-AR genes are not a frequent cause of hereditary hearing loss in the Czech Republic. This diagnostic approach permitted the clarification of HL in only one patient - two heterozygous mutations were detected in LHFPL5 gene for the first time in Central Europe. As the use of panel base MPS certainly improves the diagnostic yield, future studies should rather profit from that diagnostic strategy.

• MeSH
• dítě MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• genetické markery MeSH
• heterozygot MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• mutace * MeSH
• percepční nedoslýchavost genetika   MeSH
• proteiny vázající vápník genetika   MeSH
• proteiny genetika   MeSH
• receptory buněčného povrchu genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

INTRODUCTION: Hearing loss (HL) is the most common sensory deficit in humans. HL is an extremely heterogeneous condition presenting most frequently as a nonsyndromic (NS) condition inherited in an autosomal recessive (AR) pattern, termed DFNB. Mutations affecting the STRC gene cause DFNB type 16. Various types of mutations within the STRC gene have been reported from the U.S. and German populations, but no information about the relative contribution of STRC mutations to NSHL-AR among Czech patients is available. METHODS AND PATIENTS: Two hundred and eighty-eight patients with prelingual NSHL, either sporadic (n = 207) or AR (n = 81), who had been previously tested negative for the mutations affecting the GJB2 gene, were included in the study. These patients were tested for STRC mutations by a quantitative comparative fluorescent polymerase chain reaction (QF-PCR) assay. In addition, 31 of the 81 NSHL-AR patients were analyzed by massively parallel sequencing using one of two different gene panels: 23 patients were analyzed by multiplex-ligation probe amplification (MLPA); and 9 patients by SNP microarrays. RESULTS: Causal mutations affecting the STRC gene (including copy number variations [CNVs] and point mutations) were found in 5.5% of all patients and 13.6% of the 81 patients in the subgroup with NSHL-AR. CONCLUSION: Our results provide strong evidence that STRC gene mutations are an important cause of NSHL-AR in Czech HL patients and are probably the second most common cause of DFNB. Large CNVs were more frequent than point mutations and it is reasonable to test them first by a QF-PCR method-a simple, accessible, and efficient tool for STRC CNV detection, which can be combined by MLPA.

• MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• mutace * MeSH
• nedoslýchavost genetika   MeSH
• polymerázová řetězová reakce MeSH
• sekvenční delece MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

OBJECTIVES: 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. PATIENTS AND 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. CONCLUSION: 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.

• MeSH
• detekce genetických nosičů MeSH
• exony MeSH
• genotyp MeSH
• glutaredoxiny genetika   MeSH
• hluchota genetika   MeSH
• homozygot MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• mutace * MeSH
• pokrevní příbuzenství MeSH
• receptory pro estrogeny genetika   MeSH
• rodokmen MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH