PI * S iiyama , a deficiency gene of alpha1-antitrypsin: Evidence for the occurrence in western Japan

Abstract

Summary An alphaa-antitrypsin deficiency associated with pulmonary emphysema was investigated in a 32-year-old Japanese male. Polymerase chain reaction (PCR)-amplified fragments and dot blot hybridization with allele-specific oligonucleotide probes revealed that the patient was homozygous for a C to T transition at codon 53, resulting in the substitution of Phe 53 for Ser 5~ (PI*Siiyama). Crossedimmunoelectrophoresis after isoelectric focusing and agarose gel electrophoresis showed atypical banding patterns. PI*S~iyam, is a rare deficiency gene, but it can occur sporadically all over the Japan.

Alpha 1-antitrypsin-deficient variant Siiyama (Ser53[TCC] to Phe53[TTC]) is prevalent in Japan. Status of alpha 1-antitrypsin deficiency in Japan.

“…In contrast to this prevalence of acAT deficiency in Caucasians, only 12 cases of ai-AT deficiency have been reported in Japan (14-25; and K. Konishi, Iwate Medical University, School of Medicine, personal communication), including five cases for which the genetic defects have been elucidated, comprising one case of Mnichinan (19), two unrelated cases of Siiyama (21,22,25), a heterozygote of Mmalton (23), and a case of 14q -syndrome (18).…”

“…In the present study, it was found that five unrelated families with (I.-AT deficiency, including eight deficient individuals, shared the same genetic defects in the (I.-AT gene, resulting in every case in the (I.-AT Siiyarna gene. Moreover, another, unrelated family carrying the Siiyarna gene was detected by another group(25). These results indicate that the (I.-AT deficient variant Siiyarna is highly prevalent in Japan, being detected in seven (70070) of 10families with (I.-AT deficiency who were examined at the level of the (I.-AT gene.…”

“…One null variant, (I.-AT Nullhongkong (two nucleotides deleted within the codon for residue 318, resulting in premature termination of the (I.-ATpeptide at residue 334), was reported in a Chinese family(28). Three deficient variants were reported in Japan, including (I.-AT Siiyarna(19,(21)(22)(23)25). Using isoelectric focusing (IEF) of serum, several investigators surveyed the distribution of the (I.-AT phenotype in Asian and Pacific populations(29)(30)(31).…”

Alpha-1 Antitrypsin Deficiency with Severe Pulmonary Emphysema

“…Interestingly, this disease is quite rare in Japan, and we believe this report presents the sixteenth trait found in the Japanese population. All of the reported cases in Japan are listed in Table 1 (4,(7)(8)(9)(10)(11)(12)(13)(14)(15). While ZZ homozygote is the most common cause of AAT deficiency in Caucasians, Siiyama variant was the primary cause among the Japanese cases of AAT deficiency.…”

Compound Heterozygosity for Alpha-1-antitrypsin (Siiyama and QOclayton) in an Oriental Patient.

“…Although this deficiency is among the most commonhereditary disorders in Caucasians (1), it is very rare among Orientals; gene frequencies of deficient alleles are estimated to be extremely low. Considering all Asian countries, only 13 Japanese families and one Chinese family with alAT deficiency have been reported (3)(4)(5)(6)(7)(8)(9). Consanguineousmarriage was noted in most of these families.…”