title: A new exon created by intronic insertion of a rearranged LINE-1 element as the cause of chronic granulomatous disease.
abstract: 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 (CGD) 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.
authors.affiliation: CLB, Sanquin Blood Supply Foundation and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Meischl
authors.forename: M
authors.initials: M
authors.lastname: Boer
authors.forename: A
authors.initials: A
authors.lastname: Ahlin
authors.forename: D
authors.initials: D
authors.lastname: Roos
mesh_terms: D000328:Adult; D017398:Alternative Splicing / Q000235:genetics; D001483:Base Sequence; D002675:Child, Preschool; D005091:Exons / Q000235:genetics*; D017809:Fatal Outcome; D006105:Granulomatous Disease, Chronic / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007438:Introns / Q000235:genetics*; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics; D011995:Recombination, Genetic
chemical_list: D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases