GM08771

GM08771 Fibroblast

Description:

REFSUM DISEASE, INFANTILE FORM
PEROXISOME BIOGENESIS FACTOR 26; PEX26

Affected:

Yes

Sex:

Female

Age:

4 YR (At Sampling)

Overview

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

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)]

Characterizations

Passage Frozen

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.

Phenotypic Data

Remarks

Publications

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