Novel Mutation in the AAAS Gene in a Severely Affected Triple-A Syndrome Patient

Hansen, Morten Hartvig; Frederiksen, Anja Lisbeth; Juhl, Claus Bogh

doi:10.4172/2161-1017.1000186

Cited by 2 publications

(2 citation statements)

References 20 publications

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“…Additionally, three papers describing summary statistics were excluded, as no clear information about phenotypic and genotypic characteristics of individual patients could be discerned. Finally, data of 133 index cases (cohort 2) from 68 publications were analyzed ( 4 , 5 , 6 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , ...…”

Section: Methodsmentioning

confidence: 99%

Phenotype–genotype spectrum of AAA syndrome from Western India and systematic review of literature

Patt¹,

Koehler

Lodha

et al. 2017

Endocrine Connections

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ObjectiveTo study genotype–phenotype spectrum of triple A syndrome (TAS).MethodsRetrospective chart analysis of Indian TAS patients (cohort 1, n = 8) and review of genotyped TAS cases reported in world literature (cohort 2, n = 133, 68 publications).ResultsMedian age at presentation was 4.75 years (range: 4–10) and 5 years (range: 1–42) for cohorts 1 and 2, respectively. Alacrima, adrenal insufficiency (AI), achalasia and neurological dysfunction (ND) were seen in 8/8, 8/8, 7/8 and 4/8 patients in cohort 1, and in 99, 91, 93 and 79% patients in cohort 2, respectively. In both cohorts, alacrima was present since birth while AI and achalasia manifested before ND. Mineralocorticoid deficiency (MC) was uncommon (absent in cohort 1, 12.5% in cohort 2). In cohort 1, splice-site mutation in exon 1 (p.G14Vfs*45) was commonest, followed by a deletion in exon 8 (p.S255Vfs*36). Out of 65 mutations in cohort 2, 14 were recurrent and five exhibited regional clustering. AI was more prevalent, more often a presenting feature, and was diagnosed at younger age in T group (those with truncating mutations) as compared to NT (non-truncating mutations) group. ND was more prevalent, more common a presenting feature, with later age at onset in NT as compared to T group.ConclusionClinical profile of our patients is similar to that of patients worldwide. Alacrima is the earliest and most consistent finding. MC deficiency is uncommon. Some recurrent mutations show regional clustering. p.G14Vfs*45 and p.S255Vfs*36 account for majority of AAAS mutations in our cohort. Phenotype of T group differs from that of NT group and merits future research.

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Section: Methodsmentioning

confidence: 99%

Phenotype–genotype spectrum of AAA syndrome from Western India and systematic review of literature

Patt¹,

Koehler

Lodha

et al. 2017

Endocrine Connections

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“…While the exact function of the ALADIN protein remains mostly unclear, attempts have been made to clarify the pathogenetic mechanism of the different mutations reported, seemingly causing impaired nuclear import of DNA repair proteins and the intensification of oxidative stress status in the cell. Figure 1) 3,9,41,[61][62][63][64][65][66][67][68][69]10,[70][71][72][73][74][75][76][77][78][79]11,[80][81][82][83][84][85][86][87][88][89]12,[90][91][92][93][94][95][96][97][98][99]16,[100][101]<...>…”

Section: Oral Disorders and Other Clinical Manifestationsmentioning

confidence: 99%

Triple-A Syndrome (TAS): An In-Depth Overview on Genetic and Phenotype Heterogeneity

Pogliaghi

Cangiano

Duminuco

et al. 2020

PPL

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: Triple-A Syndrome (TAS) is a rare autosomal recessive disorder characterized by three cardinal symptoms: alacrimia, achalasia and adrenal insufficiency due to ACTH insensitivity. Various progressive neurological abnormalities and skin changes have been described in association with the syndrome. The disease is caused by mutation in the AAAS gene on chromosome 12q13. Mutations in AAAS were identified in more than 90% of individuals and families with TAS. The protein encoded by AAAS was termed ALADIN and is part of the WD repeat family of proteins, that have been found to be involved in many different functions such as protein-protein interaction, RNA processing, cytoskeleton assembly, control of cell division, signal transduction and apoptosis. Immunohistochemical analysis showed that mutated or truncated ALADIN localizes to the cytoplasm rather than to the nuclear pore complex. The exact function of ALADIN and the mechanisms that lead to the ACTH-resistant adrenal phenotype remains largely unknown. Nonetheless, recent studies provided some insights on the role of ALADIN as a member of the Nuclear Pore Complex not only implicated in the import of proteins involved in DNA repair and oxidative stress homeostasis but also in the strengthening of the mitotic spindle assembly. Early identification of the syndrome is challenging, given the rarity of the condition and high phenotypic heterogeneity even among members of the same family. In this review, we aim to summarize the current knowledge of clinical and molecular profile of patients with TAS and recommendations for the diagnosis, management, and follow-up of patients.

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Novel Mutation in the AAAS Gene in a Severely Affected Triple-A Syndrome Patient

Cited by 2 publications

References 20 publications

Phenotype–genotype spectrum of AAA syndrome from Western India and systematic review of literature

Phenotype–genotype spectrum of AAA syndrome from Western India and systematic review of literature

Triple-A Syndrome (TAS): An In-Depth Overview on Genetic and Phenotype Heterogeneity

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