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Type: Journal article
Title: The molecular basis of cystathionine b-synthase deficiency in Australian patients: Genotype-phenotype correlations and response to treatment
Author: Gaustadnes, M.
Wilcken, B.
Oliveriusova, J.
McGill, J.
Fletcher, J.
Kraus, J.
Wilcken, D.
Citation: Human Mutation, 2002; 20(2):117-126
Publisher: Wiley-Liss
Issue Date: 2002
ISSN: 1059-7794
Abstract: Cystathionine beta-synthase (CBS) deficiency is the most common cause of homocystinuria. It is inherited as an autosomal recessive trait and common clinical features are: dislocation of the optic lens, osteoporosis, mental retardation, and thromboembolism. We determined the molecular basis of CBS deficiency in 36 Australian patients from 28 unrelated families, using direct sequencing of the entire coding region of the CBS gene. The G307S and I278T mutations were the most common mutations. They were present in 19% and 18% of independent alleles, respectively. In total, seven novel and 20 known mutations were detected. Of those, the two novel missense mutations (C109R and G347S), as well as two known missense mutations (L101P and N228K), were expressed in E. Coli. All mutant proteins completely lacked catalytic activity. Furthermore, we studied the correlation between genotype and the biochemical response to pyridoxine treatment in the patients of whom 13 were pyridoxine responsive, 21 were non-responsive, and two were partially responsive. The G307S mutation always resulted in a severe non-responsive phenotype, whereas I278T resulted in a milder B6 responsive phenotype. From our results, we were also able to establish three other mild mutations: P49L, R369C, and V371M.
Keywords: Humans
Folic Acid
Cystathionine beta-Synthase
Blotting, Western
Drug Administration Schedule
DNA Mutational Analysis
Mutation, Missense
Child, Preschool
Infant, Newborn
Genetic Carrier Screening
DOI: 10.1002/humu.10104
Appears in Collections:Aurora harvest
Paediatrics publications

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