BACKGROUND AND AIMS: Allgrove (OMIM#231550) or Triple-A syndrome is a rare, autosomal recessive disorder characterized by the triad of familial adrenal insufficiency, achalasia, and alacrima. Approximately one-half of all patients with Triple-A syndrome have been shown to have mutations in the AAAS gene on chromosome 12q13, which results in loss or non-function of the encoded protein. METHODS: Five unrelated families clinically diagnosed with Allgrove Syndrome were evaluated for sequence variations in the AAAS gene. Blood samples were collected after informed and written consent was obtained. Isolated DNA derived from subjects was amplified using intronic primers. The entire sequence of the AAAS gene including regulatory region, coding regions and exon-intron boundaries were analyzed for any alteration by PCR and direct sequencing. RESULTS: In six probands of five families, four previously reported and two novel mutations were identified. Two heterozygote and homozygote mutations in exon 9 and the regulatory region, respectively, were detected in one of the probands. CONCLUSIONS: This is the first report of Triple-A syndrome from an Iranian population. Collectively, our study findings indicate that mutations scattered across the AAAS gene and upstream regulation elements. Various ethnic groups should develop a mutation database for their own rare genetic disorders. However, mutation databases should initially screen common mutated alleles. Our families present the typical triad of symptoms and the mutation spectrum is similar to the other population studied. Further study is required for phenotype-genotype correlation in the Iranian population.
BACKGROUND AND AIMS: Allgrove (OMIM#231550) or Triple-A syndrome is a rare, autosomal recessive disorder characterized by the triad of familial adrenal insufficiency, achalasia, and alacrima. Approximately one-half of all patients with Triple-A syndrome have been shown to have mutations in the AAAS gene on chromosome 12q13, which results in loss or non-function of the encoded protein. METHODS: Five unrelated families clinically diagnosed with Allgrove Syndrome were evaluated for sequence variations in the AAAS gene. Blood samples were collected after informed and written consent was obtained. Isolated DNA derived from subjects was amplified using intronic primers. The entire sequence of the AAAS gene including regulatory region, coding regions and exon-intron boundaries were analyzed for any alteration by PCR and direct sequencing. RESULTS: In six probands of five families, four previously reported and two novel mutations were identified. Two heterozygote and homozygote mutations in exon 9 and the regulatory region, respectively, were detected in one of the probands. CONCLUSIONS: This is the first report of Triple-A syndrome from an Iranian population. Collectively, our study findings indicate that mutations scattered across the AAAS gene and upstream regulation elements. Various ethnic groups should develop a mutation database for their own rare genetic disorders. However, mutation databases should initially screen common mutated alleles. Our families present the typical triad of symptoms and the mutation spectrum is similar to the other population studied. Further study is required for phenotype-genotype correlation in the Iranian population.
Authors: Luigi Mazzone; Valentina Postorino; Lavinia De Peppo; Lia Vassena; Laura Fatta; Marco Armando; Giuseppe Scirè; Marco Cappa; Stefano Vicari Journal: Case Rep Pediatr Date: 2013-04-09