Is genotype determination useful in predicting the clinical phenotype in lysosomal storage diseases?
- I. Maire
- … show all 1 hide
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
Understanding the relationship between genotype and clinical phenotype will clearly aid in the prognosis, treatment and counselling of patients with lysosomal storage diseases (LSDs). This, however, will require the establishment of widely accepted indices with which to score the severity of LSDs, as these diseases are characterized by their marked clinical heterogeneity. Even in the complete absence of a functional enzyme, presentation may be variable, depending on the patient's genetic background and on a range of epigenetic and environmental factors. Further difficulties in predicting disease severity and progression from the genotype arise from the rarity of these disorders, the low enzyme levels required for a normal phenotype and the relative lack of understanding of the pathophysiology of LSDs.
- Bijvoet AGA, van de Kamp EHM, Kroos MA, et al (1998) Generalized glycogen storage and cardiomegaly in a knockout mouse model of Pompe disease. Hum Mol Genet 7: 53–62. CrossRef
- Birot AM, Delobel B, Gronnier P, Bonnet V, Maire I, Bozon D (1996) A 5-megabase familial deletion removes the IDS and FMR-1 genes in a male Hunter patient. Hum Mutat 7: 266–268. CrossRef
- Boerkoel CF, Exelbert R, Nicastri C, et al (1995) Leaky splicing mutation in the acid maltase gene is associated with delayed onset of glycogenosis type II. Am J Hum Genet 56: 887–897.
- Brooks DA (1999) Molecular chaperones of the ER: their role in protein folding and genetic disease. Semin Cell Dev Biol 10: 441–442. CrossRef
- Bunge S, Clements PR, Byers S, Kleijer WJ, Brooks DA, Hopwood JJ (1998) Genotype-phenotype correlations in mucopolysaccharidosis type I using enzyme kinetics, immunoquantification and in vitro turnover studies. Biochim Biophys Acta 1407: 249–256.
- Conzelmann E, Sandhoff K (1983/ 84) Partial enzyme deficiencies: residual activities and the development of neurological disorders. Dev Neurosci 6: 58–71.
- Hermans MMP, De Graaff E, Kroos MA, et al (1994) The effect of a single base pair deletion (ΔT525) and a C1634T missense mutation (pro545leu) on the expression of lysosomal α-glucosidase in patients with glycogen storage disease type II. Hum Mol Genet 3: 2213–2218.
- Keeling KM, Brooks DA, Hopwood JJ, Li P, Thompson JN, Bedwell DM (2001) Gentamycinmediated suppression of Hurler syndrome stop mutations restores a low level of α-L-iduronidase activity and reduces lysosomal glycosaminoglycan accumulation. Hum Mol Genet 10: 291–299. CrossRef
- Kroos MA, Van der Kraan M, Van Diggelen OP, Kleijer WJ, Reuser AJ (1997) Two extremes of the clinical spectrum of glycogen storage disease type II in one family: a matter of genotype. Hum Mutat 9: 17–22. CrossRef
- Leinekugel P, Michel S, Conzelmann E, Sandhoff K (1992) Quantitative correlation between the residual activity of β-hexosaminidase A and the arylsulfatase A and the severity of the resulting lysosomal storage disease. Hum Genet 88: 513–523. CrossRef
- Millat G, Froissart R, Maire I, Bozon D (1997) Characterization of iduronate sulphatase mutants affecting N-glycosylation sites and the cysteine-84 residue. Biochem J 326: 243–247.
- Moran D, Galperin E, Horowitz M (1997) Identification of factors regulating the expression of the human glucocerebrosidase gene. Gene 194: 201–213. CrossRef
- Pasmanik-Chor M, Madar-Shapiro L, Stein OE, Aerts H, Gatt S, Horowitz M (1997) Expression of mutated glucocerebrosidase alleles in human cells. Hum Mol Genet 6: 887–895. CrossRef
- Raben N, Nagaraju K, Lee E, et al (1998) Targeted disruption of the acid α-glucosidase gene in mice causes an illness with critical features of both infantile and adult human glycogen storage disease type II. J Biol Chem 273: 19086–19092. CrossRef
- Scott HS, Bunge S, Gal A, Clarke LA, Morris CP, Hopwood JJ (1995) Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical, and biological implications. Hum Mutat 6: 288–302. CrossRef
- Scott HS, Nelson PV, Litjens T, Hopwood JJ, Morris CP (1993) Multiple polymorphisms within the α-L-iduronidase gene (IDUA): implications for a role in modification of MPS-I disease phenotype. Hum Mol Genet 2: 1471–1473.
- Sidransky E, Sherer DM, Ginns EI (1992) Gaucher disease in the neonate: a distinct Gaucher phenotype is analogous to a mouse model created by targeted disruption of the glucocerebrosidase gene. Pediatr Res 39: 134–141.
- Suzuki K, Proia RL, Suzuki K (1998a) Mouse models of human lysosomal diseases. Brain Pathol 8: 195–215. CrossRef
- Suzuki K, Vanier MT, Suzuki K (1998b) Induced mouse models of abnormal sphingolipid metabolism. J Biochem 124: 8–19.
- Thomas GH (1994) “Pseudodeficiencies” of lysosomal hydrolases. Am J Hum Genet 54: 934–940.
- Vervoort R, Gitzelmann R, Bosshard N, Maire I, Liebaers I, Lissens W (1998) Low ®-D-glucuronidase enzyme activity and mutations in the human beta-glucuronidase gene in mild mucopolysaccharidosis type VII, pseudodeficiency and a heterozygote. Hum Genet 102: 69–78. CrossRef
- Walkley SU (1998) Cellular pathology of lysosomal storage disorders. Brain Pathol 8: 175–193. CrossRef
- Is genotype determination useful in predicting the clinical phenotype in lysosomal storage diseases?
Journal of Inherited Metabolic Disease
Volume 24, Issue 2 Supplement, pp 57-61
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers
- Additional Links
- Industry Sectors
- I. Maire (1)
- Author Affiliations
- 1. Service de Biochimie Pédiatrique, Hôpital Debrousse, 29 Rue Soeur Bouvier, 69322 Lyon Cedex 05, France