Very long chain acyl coenzyme A dehydrogenase deficiency in a 5-month-old Korean boy: Identification of a novel mutation

Hahn, Sihoun; Lee, Eunha; Jung, Ju‐Yang; Hong, Chang-Ho; Yoon, Hye‐Ran; Rinaldo, Piero; Sims, Harold F.; Gibson, Beverly; Strauss, Arnold W.

doi:10.1016/s0022-3476(99)70030-2

Cited by 5 publications

(3 citation statements)

References 18 publications

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“…All cell lines were transformed by transfection with a vector expressing SV40 large Tantigen, as described elsewhere (Dodt et al 1995). Additionally, cell lines PBD009, PBD005, PBD106, and PBD400 were immortalized by stable transfection with a vector that constitutively expresses human telomerase (pBabePuro/hTER) (Hahn et al 1999). We cultured the cells in Dulbecco's modified Eagle medium high-glucose supplemented with 10% fetal bovine serum and 100 U penicillin and 100 mg streptomycin/ml (Gibco).…”

Section: Cell Lines Transfections and Immunofluorescencementioning

confidence: 99%

Alternative Splicing Suggests Extended Function of PEX26 in Peroxisome Biogenesis

Weller

Cajigas

Morrell

et al. 2005

The American Journal of Human Genetics

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Matsumoto and colleagues recently identified PEX26 as the gene responsible for complementation group 8 of the peroxisome biogenesis disorders and showed that it encodes an integral peroxisomal membrane protein with a single C-terminal transmembrane domain and a cytosolic N-terminus that interacts with the PEX1/PEX6 heterodimer through direct binding to the latter. They proposed that PEX26 functions as the peroxisomal docking factor for the PEX1/PEX6 heterodimer. Here, we identify new PEX26 disease alleles, localize the PEX6-binding domain to the N-terminal half of the protein (aa 29-174), and show that, at the cellular level, PEX26 deficiency impairs peroxisomal import of both PTS1- and PTS2-targeted matrix proteins. Also, we find that PEX26 undergoes alternative splicing to produce several splice forms--including one, PEX26- delta ex5, that maintains frame and encodes an isoform lacking the transmembrane domain of full-length PEX26 (PEX26-FL). Despite its cytosolic location, PEX26- delta ex5 rescues peroxisome biogenesis in PEX26-deficient cells as efficiently as does PEX26-FL. To test our observation that a peroxisomal location is not required for PEX26 function, we made a chimeric protein (PEX26-Mito) with PEX26 as its N-terminus and the targeting segment of a mitochondrial outer membrane protein (OMP25) at its C-terminus. We found PEX26-Mito localized to the mitochondria and directed all detectable PEX6 and a fraction of PEX1 to this extraperoxisomal location; yet PEX26-Mito retains the full ability to rescue peroxisome biogenesis in PEX26-deficient cells. On the basis of these observations, we suggest that a peroxisomal localization of PEX26 and PEX6 is not required for their function and that the interaction of PEX6 with PEX1 is dynamic. This model predicts that, once activated in an extraperoxisomal location, PEX1 moves to the peroxisome and completes the function of the PEX1/6 heterodimer.

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Section: Cell Lines Transfections and Immunofluorescencementioning

confidence: 99%

Alternative Splicing Suggests Extended Function of PEX26 in Peroxisome Biogenesis

Weller

Cajigas

Morrell

et al. 2005

The American Journal of Human Genetics

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“…Since 1995, when the human VLCAD c-DNA and gene were isolated and the nucleotide sequence determined [1,5,20], a number of molecular studies have been done on patients with VLCAD de®ciency [2,9,11]. More than 62 mutations are known in the VLCAD gene.…”

Section: Discussionmentioning

confidence: 99%

Milder childhood form of very long-chain acyl-CoA dehydrogenase deficiency in a 6-year-old Japanese boy

Doi¹,

Abo²,

Tateno³

et al. 2000

Eur J Pediatr

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“…The clinical presentation of VLCAD deficiency during infancy can range from a severe clinical course with metabolic acidosis, hypoketotic hypoglycemia, massive hepatic fatty infiltrates, hypertrophic cardiomyopathy, or sudden death to a mild presentation of hypoglycemia to totally asymptomatic. 68,[73][74][75][76][77][78][79][80] Several studies have demonstrated a clear genotype-phenotype relationship between the mutation with clinical phenotype. 68,[81][82][83] Infants with severe clinical presentations have mutations that result in no residual enzyme activity, whereas infants with milder presentations have mutations that result in residual enzyme activity.…”

Section: Medium Chain Acyl-coa Dehydrogenase Deficiencymentioning

confidence: 99%

Disorders of Fatty Acid Oxidation in the Era of Tandem Mass Spectrometry in Newborn Screening

Banta-Wright

Shelton

Bennett

2008

Newborn and Infant Nursing Reviews

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With recent advances in laboratory technology with tandem mass spectrometry (MS/MS), the number of infants identified with a fatty acid oxidation disorder has increased dramatically. Disorders of fatty acid oxidation comprise one of the most rapidly growing groups within the field of errors of metabolism. This review will explore the recent developments in newborn screening related to the use of tandem mass spectrometry and disorders of fatty acid oxidation.

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Very long chain acyl coenzyme A dehydrogenase deficiency in a 5-month-old Korean boy: Identification of a novel mutation

Cited by 5 publications

References 18 publications

Alternative Splicing Suggests Extended Function of PEX26 in Peroxisome Biogenesis

Alternative Splicing Suggests Extended Function of PEX26 in Peroxisome Biogenesis

Milder childhood form of very long-chain acyl-CoA dehydrogenase deficiency in a 6-year-old Japanese boy

Disorders of Fatty Acid Oxidation in the Era of Tandem Mass Spectrometry in Newborn Screening

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