GM16865

GM16865 Fibroblast from Skin, Arm

Description:

REFSUM DISEASE, INFANTILE FORM
PEROXISOME BIOGENESIS FACTOR 26; PEX26

Affected:

Yes

Sex:

Female

Age:

22 MO (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Lipid Metabolism

Biopsy Source

Arm

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Arm

Race

White

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; complementation group 8; culture set up from skin biopsy taken from the inner forearm; retinal abnormalities; significant high frequency hearing loss with bilateral hearing aids; reduced peroxisomal plasmalogen synthesis enzymes; elevated very long chain fatty acids, plasma pipecolic acid, phytanic acid, and urinary pipecolic acid; donor subject is a compound heterozygote: one allele has a point mutation of C>T at nucleotide 292 (292C>T) of the PEX26 gene resulting in an arginine to tryptophan change at codon 98 [Arg98Trp (R98W)]; the second allele has a point mutation resulting in a 1 bp insertion at nucleotide 255 in a codon for leucine (G255insT) resulting in a frameshift inducing a 28 amino acid sequence distinct from normal Pex26p

Characterizations

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase,Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

Gene

PEX26

Chromosomal Location

22q11.21

Allelic Variant 1

608666.0001; PEROXISOME BIOGENESIS DISORDER 7B; PBD7B

Identified Mutation

ARG98TRP; In a patient with neonatal adrenoleukodystrophy (NALD; 202370), Matsumoto et al. [Am. J. Hum. Genet. 73: 233-246 (2003)] identified a homozygous C-to-T transition at nucleotide 292 of the PEX26 gene, resulting in an arg98-to-trp (R98W) substitution. The mutation rendered PEX26 unstable and less able to participate in PEX6 (601498)-mediated interaction with PEX1 (602136). Transfection of wildtype PEX26 restored peroxisome biogenesis in fibroblasts from this patient. 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: R98W and a 1-bp insertion, 255insT (608666.0007), resulting in a frameshift introducing a distinct 28-amino acid sequence. Functional coexpression studies of the 2 mutations showed temperature-sensitive (30 degrees C) import of catalase and thiolase.

Gene

PEX26

Chromosomal Location

22q11.21

Allelic Variant 2

608666.0007; REFSUM DISEASE, INFANTILE FORM

Identified Mutation

1-BP INS, 255T; 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: R98W and a 1-bp insertion, 255insT (608666.0007), resulting in a frameshift introducing a distinct 28-amino acid sequence. Functional coexpression studies of the 2 mutations showed temperature-sensitive (30 degrees C) import of catalase and thiolase.

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