Mutations in eight small DFNB genes are not a frequent cause of non-syndromic hereditary hearing loss in Czech patients

• Published in: International journal of pediatric otorhinolaryngology Vol. 86; pp. 27 - 33
• Main Authors: Marková, Simona, Šafka Brožková, Dana, Meszárosová, Anna, Neupauerová, Jana, Groh, Daniel, Křečková, Gabriela, Laššuthová, Petra, Seeman, Pavel
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.07.2016
• Subjects: Adult; Calcium-Binding Proteins - genetics; Child; Czech Republic; DFNB; DFNB67; Female; Genetic Markers; Genetic Predisposition to Disease; Hearing Loss, Sensorineural - genetics; Hereditary hearing loss; Heterozygote; Humans; LHFPL5; Male; Membrane Proteins - genetics; Mutation; NSHL-AR; Otolaryngology; Pediatrics; Proteins - genetics; Receptors, Cell Surface - genetics; TMHS; Czech Republic; LHFPL5; DFNB; TMHS; hereditary hearing loss; NSHL-AR; DFNB67; Hereditary hearing loss
• ISSN: 0165-5876; 1872-8464
• DOI: 10.1016/j.ijporl.2016.04.005

Abstract 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 LHFPL-5 (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 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.