title: Mucolipidosis in a Chinese family with compound heterozygous mutations at the GNPTAB gene.
abstract: 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+1G>A in the GNPTAB gene. We determine the family as MLIII based on the DNA-test and clinical diagnoses.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Center for Human Genome Research and the College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China.
authors.forename: Tailan
authors.initials: T
authors.lastname: Zhan
authors.forename: Xiukun
authors.initials: X
authors.lastname: Cui
authors.forename: Xuenong
authors.initials: X
authors.lastname: Xing
authors.forename: An
authors.initials: A
authors.lastname: Ren
authors.forename: Guanqi
authors.initials: G
authors.lastname: Gan
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.forename: Mugen
authors.initials: M
authors.lastname: Liu
mesh_terms: D044466:Asian People; D002681:China; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D008297:Male; D009081:Mucolipidoses / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics*
chemical_list: D017855:Transferases (Other Substituted Phosphate Groups); C511050:GNPTAB protein, human