Prevalence of variants in DFNB1 locus in Serbian patients with autosomal recessive non-syndromic hearing loss
Author:
Dobric Bojana1, Radivojevic Danijela2ORCID, Jecmenica Jovana3ORCID, Fanis Pavlos4ORCID, Neocleous Vassos4ORCID, Phylactou Leonidas4, Djurisic Marina1
Affiliation:
1. Laboratory of Medical Genetics, Mother and Child Health Care Institute of Serbia “Dr Vukan Čupić”, Belgrade, Serbia 2. Laboratory of Medical Genetics, Mother and Child Health Care Institute of Serbia “Dr Vukan Čupić", Belgrade, Serbia 3. Department of Otorhinolaryngology, Mother and Child Health Care Institute of Serbia "Dr Vukan Čupić", Belgrade, Serbia 4. Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
Abstract
Hearing impairment is the most common sensorineural disorder in humans and
many genes have been identified as causable. Despite genetic heterogeneity,
a single locus, DFNB1, that contains genes GJB2 and GJB6, accounts for up to
50% of all cases. Aim of this study was to determine prevalence of
identified variants in DFNB1 locus in patients from Serbia with autosomal
recessive non-syndromic hearing loss (ARNSHL). In this study, PCR-ARMS and
direct sequencing of the GJB2 and GJB6 genes was carried out in 54 probands
and relatives from Serbia with nonsyndromic hearing loss (NSHL). In 31
patients a series of variants have been identified in the GJB2 gene. Fully
characterized genotype with bi-allelic mutations was observed in 40.74% of
the probands (22/54). The remaining probands were either identified in the
heterozygote form (9/54) or were identified with no (23/54) causing variants
for the tested genes. A total of seven different mutations were found with
following allele frequencies: c.35delG (31.48%), c.71G>A (6.48%),
c.313_326del (5.56%), c.101T>C (1.85%), c.380G>A (1.85%), c.79G>A (0.92%)
and c.269T>C (0.92%). The molecular basis of NSHL in patients from Serbia
was analyzed for the first time in this study. The results have important
implication to the development of the genetic diagnosis of deafness, genetic
counseling, and early treatment in our country. Also, our findings
contribute to the knowledge of geographic distribution of DFNB1 mutations.
Publisher
National Library of Serbia
Subject
Plant Science,Genetics
Reference29 articles.
1. BATTELLINO, S., G., RUDOLF, M., ZARGI, K., TREBUSAK PODKRAJSEK, B., PETERLIN (2011): Connexin 26 (GJB2) and connexin 30 del(GJB6-D13S1830) mutations in Slovenians with prelingual non-syndromic deafness. Int. Adv. Otol., 7(3):372-8. 2. DE CASTRO, L.S.S., A.N.R., MARINHO, E.M.R., RODRIGUES, G.C.T., MARQUES, T.A.A., DE CARVALHO, L.C.S., DA SILVA, S.E.B., D.O.S., SANTOS (2013): A study of GJB2 and delGJB6-D13S1830 mutations in Brazilian non-syndromic deaf children from the Amazon region. Braz. J. Otorhinolaryngol., 79(1):95-9. 3. DEL CASTILLO, F.J., M., RODRÍGUEZ-BALLESTEROS, A., ALVAREZ, T., HUTCHIN, E., LEONARDI, C.A., D.E., OLIVEIRA, H., AZAIEZ, Z., BROWNSTEIN, M.R., AVENARIUS, S., MARLIN, A., PANDYA, H., SHAHIN, K.R., SIEMERING, D., WEIL, W., WUYTS, L.A., AGUIRRE, Y., MARTÍN, M.A., MORENO-PELAYO, M., VILLAMAR, K.B., AVRAHAM, H.H., DAHL, M., KANAAN, W.E., NANCE, C., PETIT, R.J., SMITH, G., VAN CAMP, E.L., SARTORATO, A., MURGIA, F., MORENO, I., DEL CASTILLO (2005): A novel deletion involving the connection-30 gene, del(GJB6-D13S1854), found in trans with mutations in the GJB2 gene (connection-26) in subjects with DFNB1 nonsyndromic hearing impairment. J. Med. Genet., 42(7):588-94. 4. DEL CASTILLO, I., M., VILLAMAR, M.A., MORENO-PELAYO, F.J., DEL CASTILLO, A., ALVAREZ, D., TELLERÍA, I., MENÉNDEZ, F., MORENO (2002): A deletion involving the connexin 30 gene in nonsyndromic hearing impairment. N. Eng. J. Med., 346(4):243-9. 5. DRAGOMIR, C., A., STAN, D.T., STEFANESCU, C., SARAFOLEANU, E., SEVERIN, L., SAVU (2015): GJB2 Gene Testing, Etiologic Diagnosis and Genetic Counseling in Romanian Persons With Prelingual Hearing Loss. Int. J. Clin. Pediatr., 4(1):121-6.
|
|