title: Biotinidase deficiency: novel mutations and their biochemical and clinical correlates.
abstract: Biotinidase deficiency is a defect in the recycling of the vitamin biotin. Biotin supplementation can markedly improve the neurological and cutaneous symptoms of affected children and prevent symptoms in children identified by newborn screening or treated since birth. We have determined thirteen novel mutations in children with the disorder. Two nonsense mutations, eight single missense mutations, three allelic double missense mutations, and two are polymorphisms were identified in the biotinidase gene (BTD). One of the missense mutations, c.734G>A (p. C245Y), is the first to be reported that alters the cysteine in the putative location crucial for ester formation and binding of the biotinyl-moiety in the active site of the enzyme. These mutations add to the growing list of mutations that are helping to delineate structure/function relationships of the enzyme.
authors.affiliation: Department of Pediatrics, Connecticut Children's Medical Center and the University of Connecticut School of Medicine, Farmington, Connecticut, USA. bwolf@ccmckids.org
authors.forename: Barry
authors.initials: B
authors.lastname: Wolf
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Jensen
authors.forename: Bruce
authors.initials: B
authors.lastname: Barshop
authors.forename: Miriam
authors.initials: M
authors.lastname: Blitzer
authors.forename: Martha
authors.initials: M
authors.lastname: Carlson
authors.forename: David R
authors.initials: DR
authors.lastname: Goudie
authors.forename: Gulden Huner
authors.initials: GH
authors.lastname: Gokcay
authors.forename: Mubeccel
authors.initials: M
authors.lastname: Demirkol
authors.forename: Tolunay
authors.initials: T
authors.lastname: Baykal
authors.forename: F
authors.initials: F
authors.lastname: Demir
authors.forename: Sharon
authors.initials: S
authors.lastname: Quary
authors.forename: Ling Yu
authors.initials: LY
authors.lastname: Shih
authors.forename: Helio F
authors.initials: HF
authors.lastname: Pedro
authors.forename: Tsui-Hua H
authors.initials: TH
authors.lastname: Chen
authors.forename: Alfred E
authors.initials: AE
authors.lastname: Slonim
mesh_terms: D000483:Alleles; D001665:Binding Sites; D001710:Biotin / Q000737:chemistry; D043523:Biotinidase / Q000235:genetics*; D028921:Biotinidase Deficiency / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation
chemical_list: D001710:Biotin; D043523:Biotinidase