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Characterization of breakpoint sequences of five rearrangements in L1CAM and ABCD1 ( ALD ) genes
Author(s) -
Kutsche Kerstin,
Ressler Bernadette,
Katzera HeideGertrude,
Orth Ulrike,
GillessenKaesbach Gabriele,
Morlot Susanne,
Schwinger Eberhard,
Gal Andreas
Publication year - 2002
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.10072
Subject(s) - biology , breakpoint , genetics , alu element , gene , homologous recombination , direct repeat , exon , gene rearrangement , non homologous end joining , mutation , microbiology and biotechnology , genome , chromosomal translocation , human genome
Mutations in L1CAM are responsible for X‐linked hydrocephalus, whereas those in the ALD gene ( ABCD1 ) cause adrenoleukodystrophy. In both genes, most of the mutations reported so far are short‐length mutations and only a few patients with larger rearrangements have been documented. We have characterized three intragenic deletions of the ALD gene at the molecular level and describe here the first two L1CAM rearrangements resulting in deletion of several exons in one case and about 50 kb, including the entire gene, in the second case. At both breakpoints of an ALD deletion, Alu repeats have been found and, additionally, a short Alu region of ∼130 bp was inserted, suggesting that this rearrangement is the result of a more complex non‐allelic homologous recombination event. Only one Alu element was present at the breakpoint of the second ALD rearrangement, including a 26‐bp Alu core sequence that was suggested to be a recombinogenic hot spot. These data suggest the involvement of an Alu core sequence‐stimulated non‐homologous recombination as a possible cause for this rearrangement. Short direct repeats were identified at all putative mispaired sequences in the L1CAM breakpoints and at both breakpoints of the third ALD deletion characterized, suggesting non‐homologous (illegitimate) recombination as the molecular mechanism by which these latter deletions occurred. In conclusion, our results indicate that highly repetitive elements as well as short direct repeats are frequently involved in the formation of ALD and L1CAM gene rearrangements. Hum Mutat 19:526–535, 2002. © 2002 Wiley‐Liss, Inc.