Description:
REFSUM DISEASE, INFANTILE FORM
PEROXISOME BIOGENESIS FACTOR 26; PEX26
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases |
| Class |
Disorders of Lipid Metabolism |
|
Cell Type
|
Fibroblast
|
|
Transformant
|
Untransformed
|
|
Race
|
White
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Clinical summary/Case history
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| Passage Frozen |
14 |
| |
| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
| |
| phytanoyl-CoA dioxygenase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 1.14.11.18 |
| |
| Gene |
PEX26 |
| Chromosomal Location |
22q11.21 |
| Allelic Variant 1 |
608666.0005; REFSUM DISEASE, INFANTILE FORM |
| Identified Mutation |
MET1THR; In a patient with infantile Refsum disease (266510), Matsumoto et al.[Am. J. Hum. Genet. 73:233-246 (2003)] identified compound heterozygosity for 2 mutations in the PEX26 gene: a 2T-C transition, resulting in a met1-to-thr (M1T) substitution in the initiator met residue, and a 134T-C transition, resulting in a leu45-to-pro (L45P; 608666.0006) substitution. Functional expression studies showed that the M1T mutation allowed some catalase and thiolase import, whereas the L45P mutation had virtually no temperature-sensitive (30 degrees C) import. Coexpression of the 2 mutations resulted in temperature-sensitive import, corresponding to the milder phenotype. |
| |
| Gene |
PEX26 |
| Chromosomal Location |
22q11.21 |
| Allelic Variant 2 |
608666.0006; REFSUM DISEASE, INFANTILE FORM |
| Identified Mutation |
LEU45PRO; In a patient with infantile Refsum disease (266510), Matsumoto et al. [Am. J. Hum. Genet. 73: 233-246 (2003)] identified compound heterozygosity for 2 mutations in the PEX26 gene: a 2T-C transition, resulting in a met1-to-thr (M1T) substitution in the initiator met residue, and a 134T-C transition, resulting in a leu45-to-pro (L45P; 608666.0006) substitution. Functional expression studies showed that the M1T mutation allowed some catalase and thiolase import, whereas the L45P mutation had virtually no temperature-sensitive (30 degrees C) import. Coexpression of the 2 mutations resulted in temperature-sensitive import, corresponding to the milder phenotype. |
| Remarks |
Complementation group 8; severe developmental delay; facial dysmorphism; sensorineural hearing loss; severe visual impairment with retinitis pigmentosa; elevated serum phytanic and pipecolic acid; deficient fibroblast phytanic acid oxidase activity; increased ratio of C26/C22 very long chain fatty acids; donor subject is a compound heterozygote: allele one has a T>C transition at nucleotide 2 of the PEX26 gene (2T>C), resulting in a Met1-to-Thr substitution in the initiator Met residue [Met1Thr (M1T)]; the second allele has a T>C transition at nucleotide 134 (134T>C), resulting in a Leu45-to-Pro substitution [Leu45Pro (L45P)] |
| Weller S, Cajigas I, Morrell J, Obie C, Steel G, Gould SJ, Valle D, Alternative Splicing Suggests Extended Function of PEX26 in Peroxisome Biogenesis. Am J Hum Genet76(6):987-1007 2005 |
| PubMed ID: 15858711 |
| |
| Matsumoto N, Tamura S, Furuki S, Miyata N, Moser A, Shimozawa N, Moser HW, Suzuki Y, Kondo N, Fujiki Y, Mutations in novel peroxin gene PEX26 that cause peroxisome-biogenesis disorders of complementation group 8 provide a genotype-phenotype correlation. Am J Hum Genet73(2):233-46 2003 |
| PubMed ID: 12851857 |
| |
| Imamura A, Tsukamoto T, Shimozawa N, Suzuki Y, Zhang Z, Imanaka T, Fujiki Y, Orii T, Kondo N, Osumi T, Temperature-sensitive phenotypes of peroxisome-assembly processes represent the milder forms of human peroxisome-biogenesis disorders American journal of human genetics62:1539-43 1998 |
| PubMed ID: 9585609 |
| |
| Yajima S, Suzuki Y, Shimozawa N, Yamaguchi S, Orii T, Fujiki Y, Osumi T, Hashimoto T, Moser HW, Complementation study of peroxisome-deficient disorders by immunofluorescence staining and characterization of fused cells. Hum Genet88:491-9 1992 |
| PubMed ID: 1372585 |
| |
| Budden SS, Kennaway NG, Buist NR, Poulos A, Weleber RG, Dysmorphic syndrome with phytanic acid oxidase deficiency, abnormal very long chain fatty acids, and pipecolic acidemia: studies in four children. J Pediatr108:33-9 1986 |
| PubMed ID: 2418187 |
| |
| Weleber RG, Tongue AC, Kennaway NG, Budden SS, Buist NR, Ophthalmic manifestations of infantile phytanic acid storage disease. Arch Ophthalmol102:1317-21 1984 |
| PubMed ID: 6206835 |
| Passage Frozen |
14 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
3% |
| Medium |
Eagles Minimum Essential Medium with Earle's salts:Dulbecco's modified MEM with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
|