Mutation analysis of AAAS gene in a child with Allgrove syndrome

Objective To study the AAAS gene mutations in a child with autosomal recessive Allgrove syndrome. Methods Clinical data were collected and blood samples were obtained from the proband of Allgrove syndrome and her parents. Genomic DNA was extracted and sequenced by PCR amplification. Subclone sequencing was performed to validate the gene mutations. The disease-causing potentials of mutation genes were evaluated by the Mutation Taster, and the target protein tertiary structure was modelled by the Swiss Model. Results A new heterozygous insertion mutation(c.1347_1348insG)of exon 15 in the proband was identified and firstly reported. Other two reported mutations were detected, which were the heterozygous mutation c. 688C>T in the patient and her mother, and the homozygous mutation c. 855C>T in the proband and her parents. In addition, it was confirmed that the novel compound heterozygous mutations(c.688C>T, c. 1347_1348insG)in the AAAS gene of the proband were pathogenic mutation locus. Conclusion The heterozygous mutation(c.1347_1348insG)of AAAS gene was firstly reported. In case of the patients being clinically misdiagnosed, related-gene detection should be performed for the patients who were diagnosed with primary adrenal insufficiency during the period of infants and young childhood. (Chin J Endocrinol Metab, 2018, 34: 44-49) Key words: Allgrove syndrome; AAAS gene; Compound heterozygous mutations; ALADIN protein