A Novel <i>AAAS</i> Gene Mutation (p.R194X) in a Patient with Triple A Syndrome

Abstract

Objective: The clinical and molecular data of a patient with triple A syndrome are reported. Patient: A 21-year-old male who was diagnosed for adrenal insufficiency at the age of 2 years after a severe attack of adrenal crisis. At the age of 4 years, achalasia and alacrima were diagnosed. Puberty started at the age of 17 years. At the same time, symptoms of central, peripheral, and autonomic nervous system dysfunction were noted. Later on, at the age of 20 years, a bone age delay of 6 years and severe osteoporosis was diagnosed. Results: A compound heterozygous AAAS mutation consisting of two mutations was found: a C > T transition in exon 7 resulting in a change of arginine at amino acid position 194 into a stop codon (Arg194X) at one allele, and a C > T transition in exon 12 resulting in a change of glutamine at amino acid position 387 into a stop codon (Gln387X) on the other allele. Conclusion: The mutation in exon 7 (p.R194X) of the AAAS gene is a novel mutation which has not been found in any other family so far, whereas the second was already found in some other families. This case adds to the clinical and molecular spectrum of triple A syndrome and may provide a new insight into the functions of AAAS gene.

Neurological features in adult Triple-A (Allgrove) syndrome

“…1G-[ A, c.1331 ? 1G [ A, c.43C [ A, c.580C [ T, c.1024C [ T), but others are described here for the first time to our knowledge (c.352delT, c.1374-1176delTTCinsA, c.991T [ C, c.43C [ A, c.928_931delGTCT)[2,[11][12][13].…”

Triple A Syndrome in a Patient with Genetic Growth Hormone Insensitivity: Phenotypic Effects of Two Genetic Disorders

“…Although there is a high variability in the age of presentation and in the severity of the symptoms, most patients with triple A syndrome present with adrenal insufficiency before the age of 6 years [31]. The reason for the delayed presentation in our patient is not clear, but could be due to his IGF-I deficiency.…”

“…The mode of genetic transmission was, however, unclear as the parents were not available for analysis [30]. The p.R194X has also been reported as part of a compound heterozygous AAAS mutation (along with a second nonsense mutation, p.Q387X) in a patient with AAAS syndrome [31]. Our report, therefore, is the first full clinical and molecular description of a patient with a homozygous p.R194X mutation, indicating that this syndrome is transmitted in an autosomal recessive fashion.…”

Triple A syndrome

“…Approximately 100 cases have been reported till now. 1 We describe a 2-year-old girl with classical features of adrenal insufficiency with history of hypoglycemic seizures. She was born to second degree consanguinous parents.…”

“…Other described features of this syndrome includes Osteoporosis 1 Microcephaly 5 Short stature, 5 Dysmorphic facies 5 Delayed puberty. 1 The gene responsible for the syndrome has been identified on chromosome 12q13 and designated AAAS. 5 AAAS gene (Achalasia-Adrenal insufficiency-Alacrmia-Syndrome gene) whose mutant product protein fails to localize at the nuclear pore complexes (NPCs) which form a selective channel between the cytoplasm and the nucleus, and remains predominantly in the cytoplasm.…”