Triple A syndrome in Japan.

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Triple A syndrome is a rare autosomal recessive disorder affecting the esophagus, eyes, and adrenal glands.
• It involves the central, peripheral, and autonomic nervous systems, sometimes mimicking amyotrophic lateral sclerosis (ALS).
• The condition is caused by mutations in the ALADIN gene, a nuclear pore complex component, with few cases reported in Japan.

Purpose of the Study:

• To conduct the first nationwide survey of Triple A syndrome in Japan.
• To identify new patients and characterize their mutations.
• To investigate the cellular localization of mutant ALADIN proteins.

Main Methods:

• Nationwide survey for Triple A syndrome patients in Japan.
• Genetic analysis to identify mutations.
• Expression of GFP-fusion proteins in cultured cells to assess protein localization.

Main Results:

• Two new Japanese patients with Triple A syndrome were identified.
• One patient presented a novel mutation (p.Ser182fsX19).
• All tested mutant ALADIN proteins showed mislocalization from the nuclear pore complex to the cytoplasm.

Conclusions:

• The primary neurological manifestation in Japanese patients is progressive bulbospinal muscular atrophy, resembling motor neuron disease.
• This finding is consistent with observations in Western countries.
• The discovery of new cases indicates that Triple A syndrome may be underdiagnosed in Japan.