Mutations in eight small DFNB genes are not a frequent cause of non-syndromic hereditary hearing loss in Czech patients.
OBJECTIVE
To evaluate the contribution of eight small NSHL-AR (non-syndromic deafness, autosomal recessive) genes to hereditary hearing loss in Czech patients.


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.


CONCLUSIONS
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.
DNA Laboratory, Department of Paediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital. Electronic address: simona.markova@protonmail.ch.
Simona
S
Marková
DNA Laboratory, Department of Paediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital.
Dana
D
Šafka Brožková
DNA Laboratory, Department of Paediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital.
Anna
A
Mészárosová
DNA Laboratory, Department of Paediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital.
Jana
J
Neupauerová
Otorinolaryngology Centrum, FORTMEDICA, Prague, Czech Republic.
Daniel
D
Groh
Centre for Medical Genetics and Reproductive Medicine GENNET, Prague, Czech Republic.
Gabriela
G
Křečková
DNA Laboratory, Department of Paediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital.
Petra
P
Laššuthová
DNA Laboratory, Department of Paediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital.
Pavel
P
Seeman
D000328:Adult; D002135:Calcium-Binding Proteins / Q000235:genetics; D002648:Child; D018153:Czech Republic; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D011506:Proteins / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics
D002135:Calcium-Binding Proteins; D005819:Genetic Markers; C493788:ILDR1 protein, human; C515721:LHFPL5 protein, human; C533107:LRTOMT protein, human; D008565:Membrane Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; C085578:Ca-binding protein 2
DFNB; DFNB67; Hereditary hearing loss; LHFPL5; NSHL-AR; TMHS