Two Cases of Allgrove Syndrome with Mutations in the AAAS Gene
Department of Endocrinology and Metabolism, Fukuoka Children's Hospital, Japan.Endocrine Journal (Impact Factor: 2). 11/2004; 51(5):473-7. DOI: 10.1507/endocrj.51.473
Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of adrenal insufficiency, achalasia and alacrima. This syndrome, also known as triple A syndrome, is now known to be caused by mutations in the AAAS gene. In the present study, we report two new patients of Allgrove syndrome with mutations in the AAAS gene. Patient 1 was a 22-year-old Japanese woman, born to consanguineous parents. She was confirmed to have adrenal insufficiency at the age of 3 years and 6 months. She developed alacrima and bilateral optic nerve atrophy at the age of 8 years. She had been noticed to have dysphagia. Based on these findings, she was diagnosed as having Allgrove syndrome. Mutation analysis revealed a novel homozygous point mutation in exon 7 of her AAAS gene, changing codon 194 encoding Arg (CGA) to a stop codon (TGA) (R194X). Patient 2 was a 7-year-old Japanese boy, born to consanguineous parents. At the age of 1 year, he was noticed to be unable to produce tears. He was confirmed to have adrenal insufficiency, mental retardation and spastic diplegia at the age of 5 years and 4 months. He was tentatively diagnosed as having Allgrove syndrome, although he has never complained of dysphasia. Mutation analysis revealed a homozygous point mutation in exon 4 of his AAAS gene, changing codon 119 encoding Arg (CGA) to a stop codon (TGA) (R119X). Both of the R119X and R194X mutations are predicted to result in truncated and non-functioning ALADIN proteins, and thus the diagnosis of Allgrove syndrome was confirmed by the mutation analyses. These findings indicate that there exist significant clinical variability and mutational heterogeneities in Japanese patients with this syndrome.
Article: Triple A syndrome.Indian journal of pediatrics 07/2008; DOI:10.1007/s12098-008-0104-8
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ABSTRACT: Triple A syndrome is a rare autosomal recessive disease characterized by achalasia, alacrima, adrenocorticotrophic hormone resistant adrenal failure and some neurologic abnormalities. We report a nine year old patient with alacrima, optic atrophy and achalasia with mutation in the AAAS gene. PCR amplification of the complete coding sequence as well as the exon-intron junctions of AAAS gene was performed in DNA from the patient and his parents. AAAS gene analysis demonstrated a homozygous A to G mutation at nucleotide position 122 in exon 1 in DNA from the patient. The novel mutation described confirms the diagnosis.Ophthalmic Genetics 04/2009; 30(1):45-9. DOI:10.1080/13816810802502962 · 1.46 Impact Factor
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ABSTRACT: Adrenocorticotrophin resistance syndromes comprise familial glucocorticoid deficiency (FGD) and triple A syndrome, which are rare autosomal recessive diseases with distinct clinical features and molecular etiologies. Mutations of melanocortin-2 receptor (MC2R) have been described in segregation with FGD in 25% of patients. More recently melanocortin-2 receptor accessory protein (MRAP), a small single-transmembrane domain protein, was described as an essential protein for the traffic of MC2R and its expression on the plasma membrane. About 20% of FGD patients carry homozygous mutations of MRAP. The ALADIN protein (for alacrima/achalasia/adrenal insufficiency/neurologic disorder) was identified as the molecular basis of triple A syndrome. The elucidation of the genetic basis of the ACTH resistance syndrome has contributed to the better understanding of MC2R function. However, in some patients the molecular etiology is not yet known and awaits further genetic studies.Progress in molecular biology and translational science 12/2009; 88:155-71. DOI:10.1016/S1877-1173(09)88005-8 · 3.49 Impact Factor
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