APPLICATION OF SINGLE NUCLEOTIDE POPLYMORPHISM-BASED HAPLOTYPE ANALYSIS TO
PRENETAL MONITORING IN A PREGNANCY AT RISK FOR ORNITHINE TRASNCARBAMYLASE
DEFICIENCY
Yoshino, M1, Harada, N2, Koda, Y3, Okano Y4, Nakamura H5, Yorifuji T6.
1
Division of Gene Therapy and Regenerative Medicine, Cognitive and Molecular Research
Institute of Brain Diseases (CMRIBD), Kurume University, 2Department of Pediatrics & Child
Health, 3Depatment of Forensic Medicine and Human Genetics, Kurume UniversitySchool of
Medicine, Kurume, 4Department of Genetics, Hyogo Medical College, Nishinomiya, 5Department
of Obstetrics & Gynecology, 6Department
of Pediatrics, Osaka City General Hospital, Osaka,
Japan
Background: Conventional sequencingreveals mutation in ~80% of patients with ornithine
transcarbamylase (OTC) deficiency. Otherwise, genetic diagnosis depends on linkage analysis.
Objective: An application of single nucleotide polymorphism (SNP)-based haplotype (HT)
analysisto prenatal monitoring is presented.
Case report: A 29 year-old womanwithOTC deficiencywas found to be pregnant with male and
female fetuses. Conventional sequencing disclosed no specific mutation.She nevertheless
wanted to undergo prenatal monitoring. Amniocentesis was performed but specimen from
female fetus alonecould be obtained. Specimen from the counterpart was collected after
delivery.
Method: NineSNP’s in the OTC locus were analyzedto determine HT.
Results: Study of family members revealed that HT9 allele carried mutation, which the proband
inherited from mother. Neither newbornshad HT9 allele; thus they were determined to be
unaffected. The SNP in position 1 on the HT9 allele was discordant in the proband (A) and
mother (G). This observation was best explicable by a deletion involving this position, which
was later verified.
Conclusion: This SNP-based HT analysis is useful when specific mutation is not known. The
advantages of use of SNP’s include: it requires a short run time; it can detect intragenic
recombination or deletion, if they occurred.