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 25, 1981·Lancet·G H ElderR E DE Salamanca
Apr 14, 1984·Lancet·V KordaJ Holub
Sep 1, 1983·The Journal of Clinical Investigation·Y NordmannG Fontaine
Jun 1, 1995·European Journal of Biochemistry·S TaketaniH Inokuchi
Apr 7, 1995·The Journal of Biological Chemistry·K NishimuraH Inokuchi
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A GangulyD J Prockop
Oct 1, 1993·Postgraduate Medical Journal·R J HiftM R Moore
Oct 10, 1995·Genomics·S TaketaniH Inokuchi
Apr 12, 1996·The Journal of Biological Chemistry·J M Camadro, P Labbe
Dec 1, 1995·Human Molecular Genetics·A G RobertsG H Elder
May 1, 1996·Nature Genetics·P N MeissnerH A Dailey
Jul 1, 1996·Human Molecular Genetics·L WarnichA E Retief
Mar 1, 1996·Human Molecular Genetics·J C DeybachY Nordmann
Jan 1, 1997·Human Genetics·H LamA M Christiano
Apr 16, 1998·The Journal of Investigative Dermatology·J FrankA M Christiano
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 18, 2013·Orphanet Journal of Rare Diseases·Michela BarbaroYlva Floderus
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 16, 2003·Clinical Genetics·A WimanY Floderus
Jan 26, 2006·The British Journal of Dermatology·P Poblete-GutiérrezJ Frank
Sep 16, 1999·American Journal of Human Genetics·S D WhatleyJ C Deybach
Jul 15, 2006·Biochimica Et Biophysica Acta·Richard S AjiokaJames P Kushner
Jun 28, 2000·Molecular Genetics and Metabolism·A V CorrigallP N Meissner
Jul 31, 2013·Aquatic Toxicology·Diana Amaral MonteiroAna Lúcia Kalinin
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