A new exon created by intronic insertion of a rearranged LINE-1 element as the cause of chronic granulomatous disease

被引:85
作者
Meischl, C
de Boer, M
Åhlin, A
Roos, D
机构
[1] Univ Amsterdam, Acad Med Ctr, CLB, Sanquin Blood Supply Fdn, NL-1105 AZ Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Expt & Clin Immunol Lab, NL-1105 AZ Amsterdam, Netherlands
[3] Sachs Childrens Hosp, Stockholm, Sweden
关键词
LINE-1; chronic granulomatous disease; mutation; insertion; missplicing;
D O I
10.1038/sj.ejhg.5200523
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Long interspersed nuclear element-1 (LINE-1) or L1 elements are DNA elements present in the genome in high copy number and capable of active retrotransposition. Here we present a patient with severe chronic granulomatous disease (CCD) caused by insertion of an L1 sequence into intron 5 of the X-lined gene CYBB. Due to internal rearrangements, the insert introduced new splice sites into the intron. This resulted in a highly heterogeneous splicing pattern with introduction of two L1 fragments as new exons into the transcripts and concomitant skipping of exonic coding sequence. Because no wild-type cDNA was found, this mechanism is probably responsible for the patient's phenotype. The L1 fragment, which belongs to the Ta subset of transcriptionally active LINEs, illustrates a new mechanism by which these elements can modify the transcribed coding sequence of genes.
引用
收藏
页码:697 / 703
页数:7
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