Identification of the molecular defect in patients with peroxisomal mosaicism using a novel method involving culturing of cells at 40 degrees C: implications for other inborn errors of metabolism

Human Mutation
Jeannette GootjesRonald J A Wanders

Abstract

The peroxisome biogenesis disorders (PBDs), which comprise Zellweger syndrome (ZS), neonatal adrenoleukodystrophy, and infantile Refsum disease (IRD), represent a spectrum of disease severity, with ZS being the most severe, and IRD the least severe disorder. The PBDs are caused by mutations in one of the at least 12 different PEX genes encoding proteins involved in the biogenesis of peroxisomes. We report the biochemical characteristics and molecular basis of a subset of atypical PBD patients. These patients were characterized by abnormal peroxisomal plasma metabolites, but otherwise normal to very mildly abnormal peroxisomal parameters in cultured skin fibroblasts, including a mosaic catalase immunofluorescence pattern in fibroblasts. Since this latter feature made standard complementation analysis impossible, we developed a novel complementation technique in which fibroblasts were cultured at 40 degrees C, which exacerbates the defect in peroxisome biogenesis. Using this method, we were able to assign eight patients to complementation group 3 (CG3), followed by the identification of a single homozygous c.959C>T (p.S320F) mutation in their PEX12 gene. We also investigated various peroxisomal biochemical parameters in fibroblas...Continue Reading

References

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Citations

Jan 15, 2009·European Journal of Human Genetics : EJHG·Cindy KrauseJutta Gärtner
Sep 11, 2013·Orphanet Journal of Rare Diseases·Kevin BerendseHans R Waterham
Mar 5, 2016·Journal of Inherited Metabolic Disease·Sacha FerdinandusseRonald J A Wanders
Dec 3, 2015·Orphanet Journal of Rare Diseases·Femke C C KlouwerBwee Tien Poll-The
Mar 24, 2016·American Journal of Medical Genetics. Part a·Peter WittersEva Morava
Nov 28, 2015·Biochimica Et Biophysica Acta·Hans R WaterhamRonald J A Wanders
Aug 9, 2012·Biochimica Et Biophysica Acta·Hans R Waterham, Merel S Ebberink
Dec 14, 2019·Orphanet Journal of Rare Diseases·Feng-Juan GaoJi-Hong Wu
Aug 9, 2017·Journal of Medical Case Reports·Maria BlomqvistJorge Asin-Cayuela
Oct 31, 2020·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Maha S ZakiJoseph G Gleeson
Apr 24, 2021·The Journal of Cell Biology·Heather A BaldwinRichard J Youle
Oct 24, 2006·Biochimica Et Biophysica Acta·Steven J SteinbergHugo W Moser

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