ClinGen Dosage Sensitivity Curation Page

CBS

  • Curation Status: Complete

Location Information

Select assembly: (NC_000021.8) (NC_000021.9)
  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Evidence for gain of function phenotype
PubMed ID Description
11391481 The CBS gene on chromosome 21 is overexpressed in patients with trisomy 21. This paper (Pogribna et al., 2001; PMID: 11391481) evaluated the impact of overexpression of the CBS gene on homocysteine metabolism in children with DS and to determine whether the supplementation of trisomy 21 lymphoblasts in vitro with selected nutrients would shift the genetically induced metabolic imbalance. They found that plasma levels of cystathionine and cysteine were significantly increased in children with DS, consistent with an increase in CBS activity. The increased activity of CBS in Down syndrome significantly alters homocysteine metabolism so that the folate-dependent resynthesis of methionine is compromised. The decreased availability of homocysteine promotes the well-established 'folate trap,' creating a functional folate deficiency that may contribute to the metabolic pathology of this complex genetic disorder.