INTRAGENIC DELETION IN ORNITHINE TRANSCARBAMYLASE GENE ASSOCIATED WITH
NONHOMOLOGOUS RECOMBINATION BETWEEN AN AluSx AND MER68 REPETITIVE
SEQUNECES
Yoshino M1,2, Harada N2, Soejima M3, Koda Y3, Watanabe Y2, Okano Y4, Nakamura H5, Yorifuji T6
1
Division of Gene Therapy and Regenerative Medicine, Cognitive and Molecular Research
Institute of Brain Diseases, 2Department of Pediatrics and Child Health, 3Department of Forensic
Medicine and Human Genetics, Kurume University, Kurume, Japan, 4Department Genetics,
Hyogo College of Medicine, Nishinomiya, Japan, 5Department of Gynecology and Obstetrics,
and 6Department of Pediatrics, Osaka City General Hospital, Osaka, Japan
Background: Large deletions constitute ~7% of mutations in ornithine transcarbamylase
(OTC) gene. However, breakpoints and mechanism of such deletions have been barely studied.
Objective: To clarify breakpoints of deletion and discuss its mechanism in a family with OTC
deficiency.
Case report: The subject was a 29 year-old woman with mild OTC deficiency.
Methods: Analysis of nine SNP’s, multiplex ligation-dependent probe amplification (MLPA) and
long range PCR were performed according to respective methods.
Results and discussion: Discordance in SNP in position 1 (SNP1) in the mutation-bearing allele
between the patient (A) and mother (G) implied a deletion involving SNP1 (intron 1). MLPA
analysis indicated that exons 2, 3 and 4 existed in single copy. The stepwise approach by long
range PCR led to the detection of a 31.9 Kbp deletion. The breakpoints were located in an AluSx
sequence in intron 1 and in an MER68 sequence in intron 4, respectively. This deletion
appeared to be mediated by nonhomologous end rejoining between these two repetitive
sequences.
Conclusion: Analysis of SNP’s can provide a clue to detection of a deletion. This is the first
report of a deletion in OTC gene with breakpoints located in AluSx and MER68 repeats,
respectively.