[Alpha 1-antitrypsin deficiency in Japan]

Area of Science:

• Genetics
• Molecular Biology
• Rare Diseases

Background:

• Alpha 1-antitrypsin (alpha 1-AT) deficiency is a common hereditary disorder in Caucasians but rare in Japan.
• Only 12 cases of alpha 1-AT deficiency have been documented in Japan.

Purpose of the Study:

• To investigate the genetic basis of alpha 1-antitrypsin deficiency in the Japanese population.
• To understand the prevalence and characteristics of alpha 1-AT deficiency variants in Japan.

Main Methods:

• Genetic analysis of reported alpha 1-AT deficiency cases in Japan.
• Comparison of mutation sites between Japanese and Caucasian populations.
• Screening of Japanese volunteers for specific alpha 1-AT gene variants.

Main Results:

• Ten cases revealed genetic abnormalities: Mnichinan, Mmalton heterozygote, 7 Siiyama variants, and 1 14q-syndrome.
• The Siiyama variant is the first prevalent deficient variant identified outside Caucasian populations.
• Alanine at amino acid position 213 was absent in 193 Japanese volunteers, unlike the Z type mutation site.

Conclusions:

• The genetic landscape of alpha 1-AT deficiency in Japan includes variants like Siiyama, distinct from Caucasian populations.
• The absence of the specific alanine residue at position 213 in Japanese alpha 1-AT genes may explain the lack of reported Z type deficiency cases.
• Further research is needed to fully elucidate the prevalence and clinical impact of alpha 1-AT deficiency in Japan.