Mucolipidosis in a Chinese family with compound heterozygous mutations at the GNPTAB gene

Background: Mucopolysaccharidoses (MPS) are caused by the deficiency in the metabolism of one or more types of mucopolysaccharides or glycosaminoglycans (GAGs). Mucolipidoses (ML) are a group of genetic disorders in which both glycosaminoglycans (GAGS) and sphingolipids build up in the body. Both of MPS and ML belong to lysosomal storage diseases and show similar clinical manifestations. Distinction of these two types of diseases has not been always possible using conventional clinical diagnoses. Genetic test provides a definitive diagnosis for ML and MPS diseases. Methods: The initial clinical diagnosis had suspected the proband as either MPS or ML To verify the clinical diagnosis, linkage analysis was performed with a panel of microsatellite markers flanking 10 candidate genetic loci for mucopolysaccharidosis and 2 loci for mucolipidosis. Two-point logarithm of odds (lod) scores was calculated using Linkage Package 5.2 program. Direct DNA sequence analyses of GNPTAB in the family members were performed. Results: By using linkage and mutational analyses, we have identified that the family members contain compound heterozygous mutations of p.R364X and c.2715 + 1 G>A in the GNPTAB gene. We determine the family as MLIII based on the DNA-test and clinical diagnoses. Conclusion: Our study confirms the pathological relationship between the patients' genotype and phenotype in the clinical ML manifestation, and suggests that DNA-based diagnosis serves as a better way to define ML and MPS. (C) 2011 Elsevier B.V. All rights reserved.