title: Molecular and clinical analyses of Japanese patients with carbamoylphosphate synthetase 1 (CPS1) deficiency.
abstract: Carbamoylphosphate synthetase I deficiency (CPS1D) is a urea-cycle disorder characterized by episodes of life-threatening hyperammonemia. Correct diagnosis is crucial for patient management, but is difficult to make from clinical presentation and conventional laboratory tests alone. Enzymatic or genetic diagnoses have also been hampered by difficult access to the appropriate organ and the large size of the gene (38 exons). In this study, in order to address this diagnostic dilemma, we performed the largest mutational and clinical analyses of this disorder to date in Japan. Mutations in CPS1 were identified in 16 of 18 patients with a clinical diagnosis of CPS1D. In total, 25 different mutations were identified, of which 19 were novel. Interestingly, in contrast to previous reports suggesting an extremely diverse mutational spectrum, 31.8% of the mutations identified in Japanese were common to more than one family. We also identified two common polymorphisms that might be useful for simple linkage analysis in prenatal diagnosis. The accumulated clinical data will also help to reveal the clinical presentation of this rare disorder in Japan.
authors.affiliation: Department of Pediatrics, Kyoto University Hospital, 54 Shogoin Sakyo, Kyoto, 606-8507, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Kurokawa
authors.affiliation: Department of Pediatrics, Kyoto University Hospital, 54 Shogoin Sakyo, Kyoto, 606-8507, Japan. yorif@kuhp.kyoto-u.ac.jp.
authors.forename: Tohru
authors.initials: T
authors.lastname: Yorifuji
authors.affiliation: Department of Pediatrics, Kyoto University Hospital, 54 Shogoin Sakyo, Kyoto, 606-8507, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kawai
authors.affiliation: Department of Pediatrics, Japanese Red Cross Society, Wakayama Medical Center, Wakayama, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Momoi
authors.affiliation: Division of Metabolism, Chiba Children's Hospital, Chiba, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Nagasaka
authors.affiliation: Division of Metabolism, Chiba Children's Hospital, Chiba, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Takayanagi
authors.affiliation: Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshino
authors.affiliation: Division of Clinical and Molecular Genetics, Shinshu University Hospital, Matsumoto, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosho
authors.affiliation: Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Adachi
authors.affiliation: Department of Neonatology, Chiba Municipal Kaihin Hospital, Chiba, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Otsuka
authors.affiliation: Department of Pediatrics, Shimoshizu National Hospital, Chiba, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Division of Nephrology and Rheumatology, Department of Internal Medicine, Fukuoka University School of Medicine, Fukuoka, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Murata
authors.affiliation: Department of Internal Medicine, Kitakyushu Municipal Yahata Hospital, Kitakyushu, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Suenaga
authors.affiliation: Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Pediatrics, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Kihei
authors.initials: K
authors.lastname: Terada
authors.affiliation: Department of Pediatrics, Dokkyo University School of Medicine, Tochigi, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Shimura
authors.affiliation: Department of Pediatrics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Kiwaki
authors.affiliation: Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Shintaku
authors.affiliation: Department of Pediatrics, Kobe City General Hospital, Kobe, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Yamakawa
authors.affiliation: Department of Pediatrics, Nihon University Surugadai Hospital, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakabayashi
authors.affiliation: Department of Neurology, Institute of Neurological Sciences, Tottori University, Yonago, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Wakutani
authors.affiliation: Department of Pediatrics, Kyoto University Hospital, 54 Shogoin Sakyo, Kyoto, 606-8507, Japan.
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
mesh_terms: D044466:Asian People / Q000235:genetics; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000737:chemistry / Q000235:genetics*; D020165:Carbamoyl-Phosphate Synthase I Deficiency Disease / Q000175:diagnosis* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic
chemical_list: D002222:Carbamoyl-Phosphate Synthase (Ammonia)