Abstract
The generalised peroxisomal disorders (GPDs) Zellweger syndrome (ZS), neonatal adrenoleucodystrophy (NALD), and infantile Refsum's disease (IRD) are autosomal recessive disorders associated with a failure to assemble mature peroxisomes. We confirmed the diagnosis of a GPD in eight ZS and four IRD patients (GPD1 to GPD12) biochemically by measuring very long chain fatty acids, plasmalogen biosynthesis, and catalase solubility in skin fibroblasts. One further patient (BOX-1) had the clinical phenotype of ZS, but biochemical investigations indicated an isolated deficiency of peroxisomal β oxidation. To date a total of 10 complementation groups (CGs) for the GPDs and three further CGs for isolated β oxidation deficiencies have been identified. Most GPD patients have been shown to belong to CG-1 (Baltimore classification); among the rarer groups, CG-4 and CG-8 predominate. We performed somatic cell hybridisation experiments on strains GPD-1 to GPD-12 using plasmalogen biosynthesis as a marker for correction and found that six ZS and three IRD patients, eight of whom were of UK origin, belonged to CG-1. Strain GPD-11, a patient of UK origin with an unusual biochemical phenotype, belonged to CG-8. Strains GPD-10 and GPD-12 were derived from ZS patients of Arabian and Pakistani origin and belonged to the rarer CGs 2 and 7, respectively. Furthermore, complementation analysis using β oxidation as a marker showed that BOX-1 had an isolated deficiency of the bifunctional protein.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 295-299 |
| Number of pages | 5 |
| Journal | Journal of Medical Genetics |
| Volume | 33 |
| Issue number | 4 |
| State | Published - 1996 |
| Externally published | Yes |
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Keywords
- Generalised peroxisomal disorder
- Peroxisomal bifunctional protein
- PXR1
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
Complementation analysis in patients with the clinical phenotype of a generalised peroxisomal disorder. / Steinberg, Steven J.; Fensom, Anthony H.
In: Journal of Medical Genetics, Vol. 33, No. 4, 1996, p. 295-299.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Complementation analysis in patients with the clinical phenotype of a generalised peroxisomal disorder
AU - Steinberg, Steven J.
AU - Fensom, Anthony H.
PY - 1996
Y1 - 1996
N2 - The generalised peroxisomal disorders (GPDs) Zellweger syndrome (ZS), neonatal adrenoleucodystrophy (NALD), and infantile Refsum's disease (IRD) are autosomal recessive disorders associated with a failure to assemble mature peroxisomes. We confirmed the diagnosis of a GPD in eight ZS and four IRD patients (GPD1 to GPD12) biochemically by measuring very long chain fatty acids, plasmalogen biosynthesis, and catalase solubility in skin fibroblasts. One further patient (BOX-1) had the clinical phenotype of ZS, but biochemical investigations indicated an isolated deficiency of peroxisomal β oxidation. To date a total of 10 complementation groups (CGs) for the GPDs and three further CGs for isolated β oxidation deficiencies have been identified. Most GPD patients have been shown to belong to CG-1 (Baltimore classification); among the rarer groups, CG-4 and CG-8 predominate. We performed somatic cell hybridisation experiments on strains GPD-1 to GPD-12 using plasmalogen biosynthesis as a marker for correction and found that six ZS and three IRD patients, eight of whom were of UK origin, belonged to CG-1. Strain GPD-11, a patient of UK origin with an unusual biochemical phenotype, belonged to CG-8. Strains GPD-10 and GPD-12 were derived from ZS patients of Arabian and Pakistani origin and belonged to the rarer CGs 2 and 7, respectively. Furthermore, complementation analysis using β oxidation as a marker showed that BOX-1 had an isolated deficiency of the bifunctional protein.
AB - The generalised peroxisomal disorders (GPDs) Zellweger syndrome (ZS), neonatal adrenoleucodystrophy (NALD), and infantile Refsum's disease (IRD) are autosomal recessive disorders associated with a failure to assemble mature peroxisomes. We confirmed the diagnosis of a GPD in eight ZS and four IRD patients (GPD1 to GPD12) biochemically by measuring very long chain fatty acids, plasmalogen biosynthesis, and catalase solubility in skin fibroblasts. One further patient (BOX-1) had the clinical phenotype of ZS, but biochemical investigations indicated an isolated deficiency of peroxisomal β oxidation. To date a total of 10 complementation groups (CGs) for the GPDs and three further CGs for isolated β oxidation deficiencies have been identified. Most GPD patients have been shown to belong to CG-1 (Baltimore classification); among the rarer groups, CG-4 and CG-8 predominate. We performed somatic cell hybridisation experiments on strains GPD-1 to GPD-12 using plasmalogen biosynthesis as a marker for correction and found that six ZS and three IRD patients, eight of whom were of UK origin, belonged to CG-1. Strain GPD-11, a patient of UK origin with an unusual biochemical phenotype, belonged to CG-8. Strains GPD-10 and GPD-12 were derived from ZS patients of Arabian and Pakistani origin and belonged to the rarer CGs 2 and 7, respectively. Furthermore, complementation analysis using β oxidation as a marker showed that BOX-1 had an isolated deficiency of the bifunctional protein.
KW - Generalised peroxisomal disorder
KW - Peroxisomal bifunctional protein
KW - PXR1
UR - http://www.scopus.com/inward/record.url?scp=0029878245&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029878245&partnerID=8YFLogxK
M3 - Article
C2 - 8730284
AN - SCOPUS:0029878245
VL - 33
SP - 295
EP - 299
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
SN - 0022-2593
IS - 4
ER -