OBJECTIVETo identify the mutation of the autoimmune regulator gene (AIRE) in a Chinese family with autoimmune polyendocrinopathy syndrome type I (APS-I).

METHODSThe AIRE gene mutations were detected using PCR and direct DNA sequencing. Restriction enzyme analysis was used to confirm the mutations and bioinformatic methods were used to predict the possible impact of the mutations on the structure and function of the AIRE protein.

RESULTSA compound heterozygous mutation of A19T/R257X was detected in the proband. Her father had the A19T mutation in exon 1, but this mutation was not detected in 100 unrelated healthy individuals. Her mother had the R257X mutation in exon 6.

CONCLUSIONThis is the first report about AIRE mutations in Chinese APS-I kindred. The A19T mutation identified in this study has not been reported in the human gene mutation database (HGMD); the R257X has not been reported in Asians.

Adolescent ; Adult ; Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Exons ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Polyendocrinopathies, Autoimmune ; genetics ; Sequence Alignment ; Transcription Factors ; chemistry ; genetics

Objective To study the influence of GM1 on hyperbilirubinemia-induced brain injury in neonatal rats and its possible mechanism.Method A total of 120 7-day-old Sprague-Dawley (SD) rats were randomly assigned into normal control group (n =40),hyperbilirubinemia group (n =40) and GM1 group (n =40).According to the different duration of hyperbilirubinemia,each group was further assigned into 5 subgroups,6 h,12 h,24 h,48 h and 72 h group (n =8).The model of neonatal rat with hyperbilirubinemia was established injecting bilirubin solution (100 μg/g) intraperitoneally.GM1 (10 mg/kg) was injected intraperitoneally immediately after the model was established in GM1 group.Immunohistochemical method was used to determine the expression of Bax in hippocampus.TUNEL method was used to measure the neural cell apoptosis index (AI) in the brain.Result Six hours after the hyperbilirubinemia model was set up,the expression of Bax and AI in hyperbilirubinemia group and GM1 group were examined.The median of AI were 33.5％ and 15.4％ respectively and the average grey value of Bax positive cells were 157.4 ± 2.8 and 162.9 ± 2.3.Both apoptosis cells and the expression of Bax were gradually increasing,and peaked at 72 h after the model was established.The median of AI were 55.5％ and 35.5％ respectively,and the average grey value of Bax positive cells were 127.8 ± 3.6 and 141.5 ±2.7 in hyperbilirubinemia group and GM1 group.And the expressions of Bax and AI in the control group were nearly undetectable.The expression of Bax and AI in GM1 group were lower than hyperbilirubinemia group,but higher than the control group,the differences were statistically significant (P ＜ 0.001).Conclusion Brain cells apoptosis is influenced by hyperbilirubinemia-induced brain injury and Bax may be involved in the process.GM1 may reduce the brain damage by inhibiting the expression of Bax to reduce the apoptosis of the brain cells.