Genetic complementation studies

It is widely believed that I-cell disease (ML-II) and pseudo-Hurler polydystrophy (ML-III) are variants of the same disorder because fibroblasts from both these disorders are deficient in phosphotransferase activity. At the molecular level, the primary and most significant difference is that in I-cell disease the deficiency is essentially total, whereas in pseudo-Hurler polydystrophy there appears to be significant residual activity (approximately 10% of control values). The molecular basis for these two diseases may, however, be distinct, as evidenced by genetic complementation studies demonstrating complementation of ML-II by some ML-III fibroblasts (Mueller et al., 1983). Although two clinical presentations of I-cell disease have been described (i.e., the neonate and 6- to 12-month-old patient), correlation of the degree of deficiency of phosphotransferase activity with clinical severity in the two I-cell disease presentations remains controversial. 

The main purpose of the present study was to look with the hetero-polykaryontest (ref 1,2) for genetic complementation between different HG-PRT deficient cell strains, which had been fused and cultured in Plastic Film Dishes (PFD s ref 3,4) A radiochemical HG-PRT microassay, based on the use of the Parafilm Micro Cuvette (PMC ref 3,4) was developed, which permits the quantification of the enzyme activity at the single cell level. 

P. Hosli (1973) Inborn lysosomal disease detection of genetic heterogeneity by complementation studies. Proceedings of the "Third International Research Conference on Lysosomes in Cell Pathology",Louvain, in press. 

Barth PG, Wanders RJA, Schiitgens RBH, Staalman CR. Variant rhizomelic chondrodysplasia punctata (RCDP) with normal plasma phytanic acid clinico-biochemical delineation of a subtype and complementation studies. Am J Med Genet 1996 62(2) 164-168. 

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