Two cases of Allgrove syndrome with mutations in the AAAS gene.
ABSTRACT 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 in Japan[Show abstract] [Hide abstract]
ABSTRACT: Triple A syndrome is an autosomal recessive disease, characterized by esophageal achalasia, alacrima, and adrenal insufficiency, as well as involvement of the central, peripheral, and autonomic nervous systems. This disease mimics amyotrophic lateral sclerosis in some patients. The causative gene encodes ALADIN, a nuclear pore complex (NPC) component. Only 5 patients have been reported in Japan. We conducted the first nationwide survey of triple A syndrome. Identified mutants were expressed as GFP-fusion proteins in cultured cells. Two new patients were identified, and 1 had a novel mutation (p.Ser182fsX19). All mutant proteins tested were mislocalized from NPC to cytoplasm. The most consistent neurological manifestation of triple A syndrome in Japanese patients was progressive bulbospinal muscular atrophy with both upper and lower motor neuron involvement, which mimicked motor neuron disease, similar to that seen in patients in Western countries. The identification of the new patients suggests that more cases are undiagnosed in Japan. Muscle Nerve, 2013.Muscle & Nerve 09/2013; 48(3). DOI:10.1002/mus.23770 · 2.31 Impact Factor
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ABSTRACT: We report on a manifold advanced dual-wavelength digital holographic microscopy (DHM) configuration with a real-time measurement capability. The proposed configuration based on a polarizing separation scheme can be used for microscopic imaging polarimetry as well as dual wavelength digital holographic microscopy. In this paper, we show the feasibility of the proposed scheme by conducting the dual wavelength DHM experiments on a sample with a step height of 1.34μm nominally. An averaging technique is treated and three-dimensional (3D) topographic measurements are presented. The results obtained by the proposed polarization separation based single shot DHM approach shows it can provide a real time solution for measuring 3D profile information of small objects with excellent accuracy.Optics Communications 02/2012; 300. DOI:10.1016/j.optcom.2011.09.044 · 1.54 Impact Factor
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ABSTRACT: Abstract Background: Triple A syndrome is a rare autosomal recessive disease characterized by adrenal failure, alacrima, achalasia, and progressive neurologic symptoms. Aim: Here, we describe the clinical and genetic characteristics in a Chinese patient with novel mutations in the AAAS gene. Materials and methods: The clinical and radiologic characteristics of the patient have been fully described. The coding sequences, including exon-intron boundaries, were amplified from genomic DNA and were sequenced. Results: The clinical and radiologic findings of the patient are fully described. The sequencing of the AAAS gene detected two novel heterozygous mutations, including a c.577C>T, p.Gln193X in exon 7 and a novel frameshift mutation c.1062_1063insAC, p.Ser355fsX416 in exon 11. The testing of parents confirmed their heterozygous carrier status. Conclusions: There are significant clinical variability and mutational heterogeneities in Asian patients with this syndrome. DNA analysis is very helpful in establishing the final diagnosis of triple A syndrome, although its implication in the prediction of clinical expression and the outcome of the disorder is limited.Journal of pediatric endocrinology & metabolism: JPEM 01/2013; 26(3-4):1-3. DOI:10.1515/jpem-2012-0284 · 0.71 Impact Factor