Homozygous variegate porphyria: identification of mutations on both alleles of the protoporphyrinogen oxidase gene in a severely affected proband

The Journal of Investigative Dermatology
Jorge FrankA M Christiano

Abstract

Homozygous variegate porphyria is a severe skin and neurologic disease manifesting in early infancy, and characterized by markedly reduced levels of the penultimate enzyme in the heme biosynthetic pathway, protoporphyrinogen oxidase. We investigated the molecular basis of variegate porphyria, usually an autosomal dominantly inherited trait, in a severely affected female proband and her parents. The mutation detection strategy included heteroduplex analysis, automated sequencing, and allele specific oligonucleotide hybridization. We identified two underlying missense mutations in the protoporphyrinogen oxidase gene, consisting of a G-to-A transition in exon 6 (G169E), and a G-to-A transition in exon 10 (G358R). Our study establishes the molecular basis of "homozygous" variegate porphyria for the first time, in demonstrating that this patient is a compound heterozygote for two different missense mutations in the protoporphyrinogen oxidase gene.

References

Dec 24, 1977·Lancet·B GrandchampY Nordmann
Feb 1, 1991·The British Journal of Dermatology·L D'Alessandro GandolfoG C Topi
Aug 1, 1990·Australian and New Zealand Journal of Medicine·J CoakleyJ Connelly
Feb 1, 1990·The British Journal of Dermatology·P G NorrisJ L Hawk
Nov 1, 1987·Clinical Genetics·P MustajokiR Norio
Jun 1, 1986·Journal of the Royal Society of Medicine·G M MurphyS G Smith
Apr 14, 1984·Lancet·V KordaJ Holub
Sep 1, 1983·The Journal of Clinical Investigation·Y NordmannG Fontaine
Oct 1, 1993·Postgraduate Medical Journal·R J HiftM R Moore
Mar 1, 1996·Human Molecular Genetics·J C DeybachY Nordmann
Apr 16, 1998·The Journal of Investigative Dermatology·J FrankA M Christiano

❮ Previous
Next ❯

Citations

Oct 19, 2006·The Journal of Biological Chemistry·Hazel R CorradiK Ravi Acharya
Nov 13, 1998·Human Molecular Genetics·A G RobertsG H Elder
Jun 24, 2008·BMC Medical Genetics·María V RossettiAlcira Batlle
Jan 9, 2016·Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete·J Frank
Apr 16, 1998·The Journal of Investigative Dermatology·J FrankA M Christiano
Apr 5, 2001·The Journal of Investigative Dermatology·R KauppinenP Mustajoki
Jul 15, 2006·Biochimica Et Biophysica Acta·Richard S AjiokaJames P Kushner
Jun 28, 2000·Molecular Genetics and Metabolism·A V CorrigallP N Meissner
Mar 17, 2010·Lancet·Hervé PuyJean-Charles Deybach
Feb 24, 2001·Scandinavian Journal of Clinical and Laboratory Investigation·M von und zu Fraunberg, R Kauppinen
Oct 3, 2002·European Journal of Human Genetics : EJHG·Mikael von und zu FraunbergRaili Kauppinen
Jul 2, 2015·Current Protocols in Human Genetics·Vaithamanithi-Mudumbai Sadagopa Ramanujam, Karl Elmo Anderson
Jul 31, 2002·Photodermatology, Photoimmunology & Photomedicine·Shigeru Sassa

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.