- MeSH
- Bartterův syndrom * komplikace diagnóza MeSH
- lidé MeSH
- paralýza diagnóza etiologie MeSH
- svalová hypotonie diagnóza etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Hearing loss is the most frequent sensory disorder and is genetically extremely heterogeneous. By far the most frequent cause of nonsyndromic autosomal recessive hearing loss (AR-NSHL) are biallelic pathogenic mutations in the GJB2 gene causing DFNB1. The worldwide search for the second most common type of AR-NSHL took almost two decades. Recently reported alterations (mostly deletions) of the STRC gene, also named DFNB16, seem to be the second most frequent cause of AR-NSHL. Genetic testing of STRC is very challenging due to the highly homologous pseudogene. Anecdotal evidence from single patients shows that STRC mutations have their typical audiological findings and patients usually have moderate hearing loss. The aim of this study is to discover if audiological findings in patients with biallelic pathogenic mutations affecting STRC have the characteristic features and shape of audiological curves and if there are genotype/phenotype correlations in relation to various types of STRC mutations. METHODS: Eleven hearing loss patients with pathogenic mutations on both alleles of the STRC gene were detected during routine genetic examination of AR-NSHL patients. Audiological examination consisted of pure tone audiometry, stapedial reflexes, tympanometry and otoacoustic emission tests. RESULTS: The threshold of pure tone average (PTA) was 46 dB and otoacoustic emissions were not detectable in these DFNB16 patients. All patients were without vestibular irritation or asymmetry. CONCLUSION: Moderate sensorineural hearing loss is typical for DFNB16-associated hearing loss and there are no significant differences in audiological phenotypes among different types of mutations affecting STRC.
- MeSH
- alely MeSH
- audiometrie MeSH
- dítě MeSH
- dospělí MeSH
- genetické asociační studie MeSH
- hluchota genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- konexiny genetika MeSH
- lidé MeSH
- membránové proteiny genetika MeSH
- mezibuněčné signální peptidy a proteiny genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace genetika MeSH
- percepční nedoslýchavost diagnóza genetika MeSH
- polymerázová řetězová reakce MeSH
- sekvenční delece genetika MeSH
- sluchové testy MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Kabuki syndrome is mainly caused by dominant de-novo pathogenic variants in the KMT2D and KDM6A genes. The clinical features of this syndrome are highly variable, making the diagnosis of Kabuki-like phenotypes difficult, even for experienced clinical geneticists. Herein we present molecular genetic findings of causal genetic variation using array comparative genome hybridization and a Mendeliome analysis, utilizing targeted exome analysis focusing on regions harboring rare disease-causing variants in Kabuki-like patients which remained KMT2D/KDM6A-negative. The aCGH analysis revealed a pathogenic CNV in the 14q11.2 region, while targeted exome sequencing revealed pathogenic variants in genes associated with intellectual disability (HUWE1, GRIN1), including a gene coding for mandibulofacial dysostosis with microcephaly (EFTUD2). Lower values of the MLL2-Kabuki phenotypic score are indicative of Kabuki-like phenotype (rather than true Kabuki syndrome), where aCGH and Mendeliome analyses have high diagnostic yield. Based on our findings we conclude that for new patients with Kabuki-like phenotypes it is possible to choose a specific molecular testing approach that has the highest detection rate for a given MLL2-Kabuki score, thus fostering more precise patient diagnosis and improved management in these genetically- and phenotypically heterogeneous clinical entities.
- MeSH
- dítě MeSH
- DNA vazebné proteiny genetika MeSH
- elongační faktory genetika MeSH
- exom MeSH
- fenotyp * MeSH
- genetická heterogenita * MeSH
- genotyp * MeSH
- histondemethylasy genetika MeSH
- jaderné proteiny genetika MeSH
- krevní nemoci diagnóza genetika patofyziologie MeSH
- lidé MeSH
- lidské chromozomy, pár 14 MeSH
- malý jaderný ribonukleoprotein U5 genetika MeSH
- mandibulofaciální dysostóza genetika MeSH
- mentální retardace genetika MeSH
- mikrocefalie genetika MeSH
- mnohočetné abnormality diagnóza genetika patofyziologie MeSH
- nádorové proteiny genetika MeSH
- nádorové supresorové proteiny genetika MeSH
- obličej abnormality patofyziologie MeSH
- předškolní dítě MeSH
- proteiny nervové tkáně genetika MeSH
- receptory N-methyl-D-aspartátu genetika MeSH
- srovnávací genomová hybridizace MeSH
- ubikvitinligasy genetika MeSH
- vestibulární nemoci diagnóza genetika patofyziologie MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH