Korean J Lab Med.  2011 Oct;31(4):294-297. 10.3343/kjlm.2011.31.4.294.

Identification of Compound Heterozygous Mutation in a Korean Patient with Alpha 1-antitrypsin Deficiency

• Ko DH
• Chang HE
• Song SH
• Yoon H
• Park KU
• Song J

• KMID: 1781696
• DOI: http://doi.org/10.3343/kjlm.2011.31.4.294

Abstract

Alpha 1-antitrypsin (AAT) deficiency is a genetic disorder that primarily affects the lungs and liver. While AAT deficiency is one of the most common genetic disorders in the Caucasian population, it is extremely rare in Asians. Here, we report the case of a 36-year-old Korean woman with AAT deficiency who visited the emergency department of our hospital for the treatment of progressive dyspnea that had begun 10 years ago. She had never smoked. Chest computed tomography revealed panlobular emphysema in both lungs, which suggested AAT deficiency. The serum AAT level was 33 mg/dL (reference interval: 90-200 mg/dL). Four exons of the SERPINA1 gene, which is responsible for AAT deficiency, and their flanking regions were analyzed by PCR-direct sequencing. The patient was found to have 1 missense mutation (c.230C>T, p.Ser77Phe; Siiyama) and 1 frameshift mutation (c.1158dupC, p.Glu387ArgfsX14; QOclayton). This is the first Korean case of AAT deficiency confirmed by genetic analysis and the second case of a compound heterozygote of Siiyama and QOclayton, the first case of which was reported from Japan.

Keyword

Alpha 1-antitrypsin deficiency; Compound heterozygote; Korean

MeSH Terms

Adult
Asian Continental Ancestry Group/*genetics
Base Sequence
Exons
Female
Frameshift Mutation
Heterozygote
Humans
Mutation, Missense
Pedigree
Pulmonary Emphysema/diagnosis/radiography
Republic of Korea
Sequence Analysis, DNA
Tomography, X-Ray Computed
alpha 1-Antitrypsin/genetics
alpha 1-Antitrypsin Deficiency/diagnosis/*genetics/radiography

Figure

• 

  Fig. 1 (A) Chest radiograph of the patient shows hyperinflated lungs. (B) Chest computed tomography of the patient at the initial visit. Bilateral diffuse emphysema is observed in lungs.

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  Fig. 2 The chromatogram obtained by sequencing of SERPINA1 gene. (A) A missense mutation (c.230C>T, p.Ser77Phe) corresponds to the Siiyama allele. (B) A frameshift mutation (c.1158dupC, p.Glu387ArgfsX14) indicates the QOclayton allele.

• 

  Fig. 3 The patient's pedigree. The proband is indicated by an arrow. The number below each individual represents the alpha-1antitrypsin level in serum (mg/dL; reference interval 90-200 mg/dL). The QOclayton allele is indicated by fully filled symbols and the Siiyama allele by the symbols filled with oblique lines. The parents and children of the patient were heterozygotes for Siiyama or QOclayton, as expected. NT represents not tested.

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