Am. J. Respir. Crit. Care Med., Vol 152, No. 6, 12 1995, 2119-2126.
[Alpha 1-antitrypsin-deficient variant Siiyama (Ser53[TCC] to Phe53[TTC]) is prevalent in Japan. Status of alpha 1-antitrypsin deficiency in Japan
K Seyama, T Nukiwa, S Souma, K Shimizu and S Kira
Department of Respiratory Medicine, School of Medicine, Juntendo University, Tokyo, Japan.
In contrast to the fact that alpha 1-antitrypsin (alpha 1-AT) deficiency is
one of the most common hereditary disorders of Caucasians, deficient
variants among Orientals have been recognized to be extremely rare. Only 12
cases of alpha 1-AT deficiency have been reported in Japan, including five
cases in which the genetic defects have already been elucidated: Mnichinan
(delta Phe52[TTC] and Gly148[GGG]-->Arg148[AGG]), two unrelated cases of
Siiyama (Ser53[TCC]-- >Phe53[TTC]), a heterozygote of Mmalton (delta
Phe52[TTC]), and one additional case of 14q- syndrome (sporadic deletion of
the neighboring region of the alpha 1-AT gene locus). alpha 1-AT Siiyama is
a deficient variant originally identified in a 38-yr-old patient with
pulmonary emphysema in Japan. The amino acid substitution in this variant
occurs in a highly conserved residue of the serpin (serine protease
inhibitor) backbone (Seyama K, et al. 1991. J. Biol. Chem.
266:12627-12632). We attempted to determine whether alpha 1-AT deficiency
in Japan was caused by independent genetic defects or whether it shared
some common mutations in the alpha 1-AT gene. We examined five of seven
available families for which the genetic defects causing alpha 1-AT
deficiency have not yet been explored. When the allele-specific polymerase
chain reaction (PCR) was performed with a pair of oligonucleotide primers
having the mutated base sequence of the alpha 1-AT Siiyama allele at the 3'
end, all eight cases of alpha 1-AT deficiency among five unrelated families
turned out to be homozygous carriers of the alpha 1- AT Siiyama
mutation.(ABSTRACT TRUNCATED AT 250 WORDS)
