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1.
J Neurogenet ; 35(1): 45-57, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33825593

RESUMO

The characteristic feature of noise-induced hearing loss (NIHL) is the loss or malfunction of the outer hair cells (OHC) and the inner hair cells (IHC) of the cochlea. 90-95% of the spiral ganglion neurons, forming the cell bodies of cochlear nerve, synapse with the IHCs. Glutamate is the most potent excitatory neurotransmitter for IHC-auditory nerve synapses. Excessive release of glutamate in response to acoustic trauma (AT), may cause excitotoxicity by causing damage to the spiral ganglion neurons (SGN) or loss of the spiral ganglion dendrites, post-synaptic to the IHCs. Another neurotransmitter, GABA, plays an important role in the processing of acoustic stimuli and central regulation after peripheral injury, so it is potentially related to the regulation of hearing function and sensitivity after noise. The aim of this study is to evaluate the effect of AT on the expressions of glutamate excitotoxicity, GABA inhibition and neurosteroid synthesis genes.We exposed 24 BALB/c mice to AT. Controls were sacrificed without exposure to noise, Post-AT(1) and Post-AT(15) were sacrificed on the 1st and 15th day, respectively, after noise exposure. The expressions of various genes playing roles in glutamate, GABA and neurosteroid pathways were compared between groups by real-time PCR.Expressions of Cyp11a1, Gls, Gabra1, Grin2b, Sult1a1, Gad1, and Slc1a2 genes in Post-AT(15) mice were significantly decreased in comparison to control and Post-AT(1) mice. No significant differences in the expression of Slc6a1 and Slc17a8 genes was detected.These findings support the possible role of balance between glutamate excitotoxicity and GABA inhibition is disturbed during the post AT days and also the synthesis of some neurosteroids such as pregnenolone sulfate may be important in this balance.


Assuntos
Cóclea/metabolismo , Ácido Glutâmico/genética , Perda Auditiva Provocada por Ruído/genética , Neuroesteroides/metabolismo , Ácido gama-Aminobutírico/genética , Animais , Ácido Glutâmico/metabolismo , Células Ciliadas Auditivas Internas/metabolismo , Células Ciliadas Auditivas Externas/metabolismo , Perda Auditiva Provocada por Ruído/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ácido gama-Aminobutírico/metabolismo
2.
Mol Biol Rep ; 46(4): 3677-3690, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31006099

RESUMO

Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder due to presence of mutations in the genes involved in the metabolism of steroid hormones in adrenal gland. There are two main forms of CAH, classic form and non-classic form. While classic form stands for the severe form, the non-classic form stands for the moderate and more frequent form of CAH. The enzyme deficiencies such as 21-hydroxylase, 11-beta-hydroxylase, 3-beta-hydroxysteroid dehydrogenase, 17-alpha-hydroxylase deficiencies are associated with CAH. In this study, we aimed to investigate CYP21A2, CYP11B1, HSD3B2 genes which are associated with 21-hydroxylase, 11-beta-hydroxylase and 3-beta-hydroxysteroid dehydrogenase enzyme deficiencies, respectively, in 365 individuals by using Sanger sequencing method. We emphasized the classification of variants according their disease causing potential, and evaluated variants' frequencies including newly discovered novel variants. As a result, 32 variants of CYP21A2 including 10 novel variants, 9 variants of CYP11B1 including 3 novel variants and 6 variants of HSD3B2 including 4 novel variants were identified. The conclusions of our study showed that in Anatolia, discovery of novel variants is quite common on account of tremendous ratios of consanguineous marriages which increases the frequency of CAH. These results will contribute to the understanding of molecular pathology of the disease.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Progesterona Redutase/genética , Esteroide 11-beta-Hidroxilase/genética , Esteroide 21-Hidroxilase/genética , 3-Hidroxiesteroide Desidrogenases/metabolismo , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , Bases de Dados Genéticas , Feminino , Estudos de Associação Genética , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Esteroide 11-beta-Hidroxilase/metabolismo , Esteroide 17-alfa-Hidroxilase/metabolismo , Esteroide 21-Hidroxilase/metabolismo , Turquia , Adulto Jovem
4.
Eur J Med Genet ; 58(12): 689-94, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26518167

RESUMO

Bardet-Biedl Syndrome (BBS) is a rare, autosomal-recessive ciliopathy characterized by obesity, rod-cone dystrophy, postaxial polydactyly, renal abnormalities, genital abnormalities and learning difficulties. To date, mutations in 21 different genes have been described as being responsible for BBS. Recently sequential gene sequencing has been replaced by next generation sequencing (NGS) applications. In this study, 15 patients with clinically diagnosed BBS were investigated using a next generation sequencing panel which included 17 known BBS causing genes (BBS1, BBS2, ARL6, BBS4, BBS5, MKKS, BBS7, TTC8, BBS9, BBS10, TRIM32, BBS12, MKS1, NPHP6, WDPCP, SDCCAG8, NPHP1). A genetic diagnosis was achieved in 13 patients (86.6%) and involved 9 novel and 3 previously described pathogenic variants in 6 of 17 BBS causing genes. BBS10 and BBS1 were the most commonly involved genes with frequencies of 31% and 23% respectively. Three of the 13 patients had an affected sibling. All affected siblings were found to be homozygous for the mutation detected in the proband. No evidence of triallelic inheritance was detected. Although limited association between certain genes and phenotypic features has been observed in this study, it is considered that additional studies are needed to better characterize the genotype-phenotype correlation of BBS. Our results demonstrate that NGS panels are feasible and effective method for providing high diagnostic yields in the diseases caused by multiple genes such as BBS.


Assuntos
Síndrome de Bardet-Biedl/diagnóstico , Síndrome de Bardet-Biedl/genética , Estudos de Associação Genética , Testes Genéticos , Mutação , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Testes Genéticos/métodos , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Fenótipo , Adulto Jovem
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