Brito Vinicius Nahime, Mendonca Berenice Bilharinho, Guilhoto Laura M F F, Freitas Karina Cocco Monteiro, Arnhold Ivo J Prado, Latronico Ana Claudia
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Disciplina de Endocrinologia e Metabologia, Avenue Dr. Eneas de Carvalho Aguiar, 155-2 andar Bloco 6, 05403900 Sao Paulo, Brazil.
J Clin Endocrinol Metab. 2006 Jun;91(6):2432-6. doi: 10.1210/jc.2005-2657. Epub 2006 Mar 28.
gamma-Aminobutyric acid (GABA) is a dominant inhibitory neurotransmitter involved in the modulation of brain electric activity and puberty onset in primates. GABA inhibitory effects on GnRH neurons are mainly mediated by GABA-A receptor alpha1-subunit.
The objective of this study was to investigate functional mutations or polymorphisms of the GABA-A receptor alpha1-subunit gene (GABRA1) in girls with idiopathic gonadotropin-dependent precocious puberty (GDPP) with and without electroencephalographic (EEG) abnormalities.
The entire coding region of GABRA1 was sequenced in all patients. Two known GABRA1 polymorphisms were investigated by GeneScan software analysis or enzymatic restriction. Seventy-three normal women were used as controls for genetic study. EEG tracings were recorded in 23 girls with GDPP and 17 girls with adequate pubertal development.
The study was performed at a university hospital.
Thirty-one girls from 28 unrelated families with idiopathic GDPP were studied.
Automatic sequencing revealed no functional mutations in girls with GDPP. Seven different GABRA1 polymorphisms, including two exonic (156T>C and 1323G>A) and five intronic [IVS2-712(GT)n, IVS3+12A>T, IVS8+45T>G, IVS9+76A>G, and IVS10+15G>A], were found in GDPP girls and controls. Abnormal EEG tracings were found in 26% of 23 girls with GDPP, two of them with epilepsy. The genotype and allele frequencies of the GABRA1 polymorphisms were not statistically different between unrelated GDPP girls and controls or between GDPP girls with or without EEG abnormalities.
GABRA1 functional mutations or polymorphisms are not associated with the intrinsic mechanism of GDPP in girls with and without EEG abnormalities.
γ-氨基丁酸（GABA）是一种主要的抑制性神经递质，参与调节灵长类动物的脑电活动和青春期启动。GABA对促性腺激素释放激素（GnRH）神经元的抑制作用主要由GABA-A受体α1亚基介导。
本研究旨在调查伴或不伴脑电图（EEG）异常的特发性促性腺激素依赖性性早熟（GDPP）女孩中GABA-A受体α1亚基基因（GABRA1）的功能突变或多态性。
对所有患者的GABRA1整个编码区进行测序。通过基因扫描软件分析或酶切研究两个已知的GABRA1多态性。73名正常女性作为遗传研究的对照。对23名GDPP女孩和17名青春期发育正常的女孩进行EEG描记。
该研究在一家大学医院进行。
研究了来自28个无关家庭的31名患有特发性GDPP的女孩。
自动测序显示GDPP女孩中无功能突变。在GDPP女孩和对照中发现了7种不同的GABRA1多态性，包括2种外显子多态性（156T>C和1323G>A）和5种内含子多态性[IVS2-71（GT）n、IVS3+12A>T、IVS8+45T>G、IVS9+76A>G和IVS10+15G>A]。23名GDPP女孩中有26%的EEG描记异常，其中2名患有癫痫。GABRA1多态性的基因型和等位基因频率在无关的GDPP女孩与对照之间，或有或无EEG异常的GDPP女孩之间无统计学差异。
GABRA1功能突变或多态性与伴或不伴EEG异常的女孩GDPP的内在机制无关。
