Abstract
Screening for mutations of the cystathionine-β-synthase (CBS) gene of homocystinuric patients we detected a splice site mutation (A1224-2C) which results in skipping of an entire 135bp exon. This mutation was reported recently by Kozich and Kraus (Hum.Mut.1,113-123;1992) and found to be associated with vitamnin B6-responsiveness in a compound heterozygous patient with mild clinical course. We established a SSCP assay to screen for this distinct splice site mutation of the CBS gene. So far, we have detected this mutation on 5 out of 28 (17.8%) affected chromosomes from nonrelated homocystinuric patients. Three patients were compound heterozygous. One male offspring of non-consanguinous parents of German origin was homozygous. In contrast to the patient described by Kozich and Kraus, this patient was clearly nonresponsive even when treated with high dose vitamin B6. He showed a severe clinical phenotype with early ocular involvement and mental retardation. Two of the three compound heterozygotes detected were also vitamin B6 nonresponders with severe phenotypes. From this we conclude that the splice site mutation A1224-2C represents a frequent defect of the CBS gene causing homocystinuria which is non-responsive to vitamin B6 treatment. Only when combined with certain other mutations in compound heterozygotes, this second allel may contribute to a milder phenotype and confer vitamin B6 responsiveness.
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Koch, H., Ullrich, K., Deufel, T. et al. 111 A HIGHLY PREVALENT SPLICE SITE MUTATION IN THE CYSTATHIONINE BT-SYNTHASE GENE IS ASSOCIATED WITH POOR VITAMIN B6 RESPONSE IN HOMOCYSTINURIA. Pediatr Res 36, 21 (1994). https://doi.org/10.1203/00006450-199407000-00111
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DOI: https://doi.org/10.1203/00006450-199407000-00111