title: Identification of a genetic mutation in a family with fructose-1,6- bisphosphatase deficiency.
abstract: Fructose-1,6-bisphosphatase deficiency is an inheritable disorder of gluconeogenesis. Sequence analysis of the cDNA of the fructose-1,6-bisphosphatase mRNA isolated from monocytes from a girl with this disease and her consanguineous parents revealed that the patient and her parents were a homozygote and heterozygotes for an insertion of one G residue at G957GGGG961, respectively. This mutation resulted in translation of a truncated enzyme protein, and the mutant protein showed no fructose-1,6- bisphosphatase activity in an overexpression experiment in Escherichia coli. However, this mutation is located in a region of the amino acid sequence which is not well conserved among mammals. A mutagenized clone was prepared from the normal clone. The extents of substitutions and deletions of the amino acid sequence were predicted to be less in the mutagenized protein than in the mutant protein. This mutagenized clone also expressed no fructose-1,6-bisphosphatase activity, although both of two normal clones from control monocytes and a control liver sample expressed an apparently normal level of fructose-1,6-bisphosphatase activity. Thus, this mutation is concluded to be responsible for fructose-1,6-bisphosphatase deficiency in this patient.
authors.affiliation: Department of Pediatrics, Fukui Medical School, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kikawa
authors.forename: M
authors.initials: M
authors.lastname: Inuzuka
authors.forename: B Y
authors.initials: BY
authors.lastname: Jin
authors.forename: S
authors.initials: S
authors.lastname: Kaji
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Shigematsu
authors.forename: A
authors.initials: A
authors.lastname: Nakai
authors.forename: A
authors.initials: A
authors.lastname: Taketo
authors.forename: T
authors.initials: T
authors.lastname: Ohura
authors.forename: H
authors.initials: H
authors.lastname: Mikami
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D003241:Consanguinity; D017931:DNA Primers; D005260:Female; D015319:Fructose-1,6-Diphosphatase Deficiency / Q000201:enzymology / Q000235:genetics*; D006597:Fructose-Bisphosphatase / Q000235:genetics*; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009679:Nuclear Family; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D006597:Fructose-Bisphosphatase