Five cases of isolated glycerol kinase deficiency, including two families: failure to find genotype:phenotype correlation
- aHuman Molecular Genetics Group, University of Cambridge, Department of Pathology, Tennis Court Road, Cambridge CB2 1QP, UK, bDepartment of Medical Genetics, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB9 2ZB, UK, cThe Willink Biochemical Genetics Unit, The Royal Manchester Children's Hospital, Pendlebury, Manchester M27 1HA, UK
- Dr Affara,na{at}mole.bio.cam.ac.uk
- Revised 22 December 1999
- Accepted 26 January 2000
Abstract
Little is understood of the genotype/phenotype correlations in X linked glycerol kinase deficiency (GKD) where most cases are caused by extensive deletions of Xp21, which often include genes flanking theGK locus. Few cases of isolated GKD have been investigated where the phenotype is not influenced by neighbouring genes. In this paper, we present the mutation data from four 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 chain, one insertion, and an amino acid substitution. Phenotypic variation was observed in two families, where there was more than one affected subject carrying the same mutation, confirming previous studies that suggest there is no correlation between disease severity and genotype. Furthermore, the nature of the mutation in different families does not appear to influence the spectrum of phenotypic variation. In addition, one coding polymorphism in exon 3 has been found. The characterisation of the gene structure has been completed and shows that instead of 19 there are 21 exons.
