Five cases of isolated glycerol kinase deficiency, including two families:failure to find genotype : phenotype correlation

Little is understood of the genotype/phenotype correlations in X linked gly cerol kinase deficiency (GKD) where most cases are caused by extensive dele tions of Xp21, which often include genes flanking the GK locus. Few cases o f isolated GKD have been investigated where the phenotype is not influenced by neighbouring genes. In this paper, we present the mutation data from fo ur confirmed and one suspected case of non-deletion, isolated, X linked GKD and therefore extend the base of patients that can allow an assessment of genotype/phenotype correlations for this disease. The mutations found were two terminations leading to premature truncation of the GK polypeptide chai n, one insertion, and an amino acid substitution. Phenotypic variation was observed in two families, where there was more than one affected subject ca rrying the same mutation, confirming previous studies that suggest there is no correlation between disease severity and genotype. Furthermore, the nat ure of the mutation in different families does not appear to influence the spectrum of phenotypic variation. In addition, one coding polymorphism in e xon 3 has been found. The characterisation of the gene structure has been c ompleted and shows that instead of 19 there are 21 exons.