J Korean Med Sci.  2004 Feb;19(1):123-126. 10.3346/jkms.2004.19.1.123.

X-linked Severe Combined Immunodeficiency Syndrome: The First Korean Case with gamma c Chain Gene Mutation and Subsequent Genetic Counseling

• Jo EK
• Kumaki S
• Wei D
• Tsuchiya S
• Kanegane H
• Song CH
• Noh HY
• Kim YO
• Kim SY
• Chung HY
• Kim YH
• Kook H

• KMID: 1785705
• DOI: http://doi.org/10.3346/jkms.2004.19.1.123

Abstract

X-linked severe combined immunodeficiency (X-SCID) is a rare, life-threatening immune disorder, caused by mutations in the gamma c chain gene, which encodes an essential component of the cytokine receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21. A 13-month-old boy with recurrent infections who had reduced serum immunoglobulin levels and decreased numbers of CD3, CD16/56 cells was evaluated for gamma c chain gene mutation and protein expression. The patient had a C-to-T point mutation at nucleotide position 690, one of the hot spots, resulting in a single amino acid substitution of cysteine for arginine (R226C), as determined by direct sequencing and PCR-RFLP. The patient's mother was a heterozygous carrier. Percutaneous umbilical cord blood sampling was performed at the 6-month of gestation in a subsequent pregnancy. As the immunophenotype of the fetus showed an identical pattern, the pregnancy was terminated and genetic analysis of the abortus confirmed recurrence. This is the first report of the molecular diagnosis of X-SCID in Korea. Genetic analysis of the gamma c chain gene is useful for definite diagnosis and genetic counseling for X-SCID.

Keyword

Severe Combined Immunodeficiency; Genetic Diseases, X-linked; Mutation; Genetic Counseling; Korea

MeSH Terms

Arginine/chemistry
Cysteine/chemistry
DNA/metabolism
DNA Mutational Analysis
Female
Flow Cytometry
Genetic Counseling/*methods
Heterozygote
Human
Immunoglobulins/metabolism
Immunophenotyping/methods
Korea
*Linkage (Genetics)
Male
*Mutation
Pedigree
Point Mutation
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Receptors, Immunologic/*genetics
Sequence Analysis, DNA
Severe Combined Immunodeficiency/*diagnosis/*genetics
Support, Non-U.S. Gov't
Time Factors
*X Chromosome

Figure

• 

  Fig. 1 Pedigree and results of flow cytometric analyses of the X-SCID family in this study. (A) Pedigree of the family. The closed square and the closed lozenge indicate the patient and the male fetus with X-SCID, respectively. The dotted circle indicates the carrier state. *, male fetus therapeutically aborted after immunophenotyping and genetic analysis. (B) Flow cytometric analysis of the patient and his mother. The level of γc chain expression in PBMCs was significantly reduced in the patient as compared with his mother. The level of γc chain expression was evaluated by flow cytometric analysis following immunostaining with mAb TUGh4.

• 

  Fig. 2 Sequence analysis showing a missense mutation of the common γc chain gene (γc chain) in an X-SCID family. (A) Genomic sequences encompassing a point mutation (C to T) in exon 5 of the γc chain gene from the patient, carrier (mother), and normal control (father) are shown. Arrow, C-to-T transversion. (B) RFLP analysis of the γc chain gene exon 5. Lanes 1 and 2, patient; Lanes 3 and 4, mother; Lanes 5 and 6, normal control. Lanes 1, 3, and 5 show the DNA fragments before restriction enzyme treatment, and Lanes 2, 4, and 6 show the DNA fragments after restriction enzyme treatment. *, Carrier; standard size markers, as indicated on the side. (C) RFLP analysis of amniotic cells. Lanes 1 and 2, fetus; Lanes 3 and 4, normal control. Lanes 1 and 3 show the DNA fragments before restriction enzyme treatment, and Lanes 2 and 4 show the DNA fragments after restriction enzyme treatment.

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