title: Novel mutations in five Japanese patients with 3-methylcrotonyl-CoA carboxylase deficiency.
abstract: Isolated 3-methylcrotonyl-CoA carboxylase (MCC) deficiency appears to be the most frequent organic aciduria detected in tandem mass spectrometry (MS/MS) screening programs in the United States, Australia, and Europe. A pilot study of newborn screening using MS/MS has recently been commenced in Japan. Our group detected two asymptomatic MCC deficiency patients by the pilot screening and collected data on another three MCC deficiency patients to study the molecular bases of the MCC deficiency in Japan. Molecular analyses revealed novel mutations in one of the causative genes, MCCA or MCCB, in all five of the patients: nonsense and frameshift mutations in MCCA (c.1750C > T/c.901_902delAA) in patient 1, nonsense and frameshift mutations in MCCB (c.1054_1055delGG/c.592C > T) in patient 2, frameshift and missense mutations in MCCB (c.1625_1626insGG/c.653_654CA > TT) in patient 3, a homozygous missense mutation in MCCA (c.1380T > G/ 1380T > G) in patient 4, and compound heterozygous missense mutations in MCCB (c.569A > G/ c.838G > T) in patient 5. No obvious clinical symptoms were observed in patients 1, 2, and 3. Patient 4 had severe neurological impairment and patient 5 developed Reye-like syndrome. The increasing use of MS/MS newborn screening in Japan will further clarify the clinical and genetic heterogeneity among patients with MCC deficiency in the Japanese population.
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Uematsu
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Sakamoto
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sugawara
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
authors.forename: Naonori
authors.initials: N
authors.lastname: Kumagai
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Morimoto
authors.affiliation: Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ihara
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshino
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Japan.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Research Institute of Medical Mass Spectrometry, Kurume University School of Medicine, 67 Asahimachi, Kurume, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Inokuchi
authors.affiliation: Department of Pediatrics, St Mary's Hospital, 422 Tsubukuhonmachi, Kurume, Japan.
authors.forename: Takato
authors.initials: T
authors.lastname: Yokoyama
authors.affiliation: Department of Pediatrics, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Kiwaki
authors.affiliation: Department of Pediatrics, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto, Japan.
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Pediatrics, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Endo
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tsuchiya
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan. tohura@mail.tains.tohoku.ac.jp.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ohura
mesh_terms: D019735:Carbon-Carbon Ligases / Q000172:deficiency / Q000235:genetics*; D016368:Frameshift Mutation; D006801:Humans; D007231:Infant, Newborn; D007564:Japan; D009154:Mutation; D020125:Mutation, Missense; D015997:Neonatal Screening / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D019735:Carbon-Carbon Ligases; C021573:methylcrotonoyl-CoA carboxylase