CONTEXT: 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. OBJECTIVE: 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. DESIGN: 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. SETTING: The study was performed at a university hospital. PATIENTS: Thirty-one girls from 28 unrelated families with idiopathic GDPP were studied. RESULTS: 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. CONCLUSIONS: GABRA1 functional mutations or polymorphisms are not associated with the intrinsic mechanism of GDPP in girls with and without EEG abnormalities.
CONTEXT: 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. OBJECTIVE: 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. DESIGN: 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. SETTING: The study was performed at a university hospital. PATIENTS: Thirty-one girls from 28 unrelated families with idiopathic GDPP were studied. RESULTS: 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. CONCLUSIONS:GABRA1 functional mutations or polymorphisms are not associated with the intrinsic mechanism of GDPP in girls with and without EEG abnormalities.
Authors: L G Silveira; S D Noel; A P Silveira-Neto; A P Abreu; V N Brito; M G Santos; S D C Bianco; W Kuohung; S Xu; M Gryngarten; M E Escobar; I J P Arnhold; B B Mendonca; U B Kaiser; A C Latronico Journal: J Clin Endocrinol Metab Date: 2010-03-17 Impact factor: 5.958