Homocystinuria caused by CBS mutations

Abstract

Homocystinuria is a rare, autosomal recessive genetic disease, which is typically caused by deficiency in cystathionine beta-synthase (CBS) activity, a pyridoxine (vitamin B6)- dependent enzyme. A deficiency of CBS due to mutations in the CBS gene causes metabolic complications and an accumulation of homocysteine, leading to an array of symptoms: neuropathy, anemia, seizures, depression, confusion, or a weakened immune system. In this study, primers were designed to target specific exons within the CBS gene, including intronic sequences. PCR and sequencing of DNA were used to search for mutations in the CBS gene, both known and novel, in multiple cell lines drawn from individuals diagnosed with homocystinuria. As these cell lines are a widely available resource and can be used to test the physiological consequences of specific mutations, identification of the mutations present is critical for understanding the linkage between changes in DNA and cellular perturbations. Furthermore, the collective data could be valuable in interpreting the results of genetic testing to potentially predict symptoms in late-onset scenarios, or to correlate current symptoms to CBS mutations. In addition to potential relevance for treatment, this could help provide affected individuals with understanding and awareness of their disease and how to cope with the symptoms.