Molecular and clinical analyses of Japanese patients with carbamoylphosphate synthetase 1 (CPS1) deficiency.
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.
Kurokawa
Keiji
K
Department of Pediatrics, Kyoto University Hospital, 54 Shogoin Sakyo, Kyoto, 606-8507, Japan.
Yorifuji
Tohru
T
Department of Pediatrics, Kyoto University Hospital, 54 Shogoin Sakyo, Kyoto, 606-8507, Japan. yorif@kuhp.kyoto-u.ac.jp.
Kawai
Masahiko
M
Department of Pediatrics, Kyoto University Hospital, 54 Shogoin Sakyo, Kyoto, 606-8507, Japan.
Momoi
Toru
T
Department of Pediatrics, Japanese Red Cross Society, Wakayama Medical Center, Wakayama, Japan.
Nagasaka
Hironori
H
Division of Metabolism, Chiba Children's Hospital, Chiba, Japan.
Takayanagi
Masaki
M
Division of Metabolism, Chiba Children's Hospital, Chiba, Japan.
Kobayashi
Keiko
K
Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Yoshino
Makoto
M
Department of Pediatrics, Kurume University School of Medicine, Kurume, Japan.
Kosho
Tomoki
T
Division of Clinical and Molecular Genetics, Shinshu University Hospital, Matsumoto, Japan.
Adachi
Masanori
M
Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
Otsuka
Harumi
H
Department of Neonatology, Chiba Municipal Kaihin Hospital, Chiba, Japan.
Yamamoto
Shigenori
S
Department of Pediatrics, Shimoshizu National Hospital, Chiba, Japan.
Murata
Toshiaki
T
Division of Nephrology and Rheumatology, Department of Internal Medicine, Fukuoka University School of Medicine, Fukuoka, Japan.
Suenaga
Akihito
A
Department of Internal Medicine, Kitakyushu Municipal Yahata Hospital, Kitakyushu, Japan.
Ishii
Tsutomu
T
Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.
Terada
Kihei
K
Department of Pediatrics, Kawasaki Medical School, Kurashiki, Japan.
Shimura
Naoto
N
Department of Pediatrics, Dokkyo University School of Medicine, Tochigi, Japan.
Kiwaki
Kohji
K
Department of Pediatrics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Shintaku
Haruo
H
Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan.
Yamakawa
Masaru
M
Department of Pediatrics, Kobe City General Hospital, Kobe, Japan.
Nakabayashi
Hiroki
H
Department of Pediatrics, Nihon University Surugadai Hospital, Tokyo, Japan.
Wakutani
Yosuke
Y
Department of Neurology, Institute of Neurological Sciences, Tottori University, Yonago, Japan.
Nakahata
Tatsutoshi
T
Department of Pediatrics, Kyoto University Hospital, 54 Shogoin Sakyo, Kyoto, 606-8507, Japan.
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
D002222:Carbamoyl-Phosphate Synthase (Ammonia)