Biotinidase deficiency: novel mutations and their biochemical and clinical correlates.
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.
Wolf
Barry
B
Department of Pediatrics, Connecticut Children's Medical Center and the University of Connecticut School of Medicine, Farmington, Connecticut, USA. bwolf@ccmckids.org
Jensen
Kevin P
KP
Barshop
Bruce
B
Blitzer
Miriam
M
Carlson
Martha
M
Goudie
David R
DR
Gokcay
Gulden Huner
GH
Demirkol
Mubeccel
M
Baykal
Tolunay
T
Demir
F
F
Quary
Sharon
S
Shih
Ling Yu
LY
Pedro
Helio F
HF
Chen
Tsui-Hua H
TH
Slonim
Alfred E
AE
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
D001710:Biotin; D043523:Biotinidase