Biochemical and computational analyses of two phenotypically related GALT mutations (S222N and S135L) that lead to atypical galactosemia.

ABSTRACT: Galactosemia is a metabolic disorder caused by mutations in the GALT gene [1,2]. We encountered a patient heterozygous for a known pathogenic H132Q mutation and a novel S222N variant of unknown significance [3]. Reminiscent of patients with the S135L mutation, our patient had loss of GALT enzyme activity in erythrocytes but a very mild clinical phenotype [3-8]. We performed splicing experiments and computational structural analyses to investigate the role of the novel S222N variant. Alamut software data predicted loss of splicing enhancers for the S222N and S135L mutations [9,10]. A cDNA library was generated from our patient׳s RNA to investigate for splicing errors, but no change in transcript length was seen [3]. In silico structural analysis was performed to investigate enzyme stability

SUBMITTER: Cocanougher B 

PROVIDER: S-EPMC4509990 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature