Selective IgG2 deficiency due to a point mutation causing abnormal splicing of the Cgamma2 gene.

Abstract:

:The mechanism underlying selective IgG subclass deficiency is largely unknown in humans. We have previously reported the acquisition of a complete IgG2 deficiency in a leukemia patient after bone marrow transplantation. Southern blot analysis showed a deletion including the Cgamma2 and Cgamma4 genes on one chromosome in the donor, suggesting that the remaining Cgamma2 gene allele was silent. In the patient and his two IgG2 deficient brothers, the silent Cgamma2 gene showed both germ-line transcription and switch recombination and no structural defects were found in the intronic promoter or the switch region of the gene. However, an A-->G transition in the fourth nucleotide in the 5' portion of intron 1 was identified. Transfection of artificial constructs into the human B cell lines demonstrated that this A-->G transition inactivated the normal splice site, and instead, a cryptic splice site in the CH1 exon was used in RNA post-transcriptional processing, leading to a 16 bp deletion of the gamma2 CH1 exon. This aberrantly spliced RNA that is mostly derived from germ-line transcription in vivo was also detected in both homozygous and heterozygous individuals carrying this mutation. These findings suggest a novel genetic mechanism as the cause of IgG subclass deficiency in selected patients.

journal_name

Int Immunol

journal_title

International immunology

authors

Zhao Y,Pan-Hammarström Q,Zhao Z,Wen S,Hammarström L

doi

10.1093/intimm/dxh192

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

95-101

issue

1

eissn

0953-8178

issn

1460-2377

pii

dxh192

journal_volume

17

pub_type

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