Human Genetics

, Volume 99, Issue 1, pp 126–129 | Cite as

Molecular basis of variegate porphyria: a de novo insertion mutation in the protoporphyrinogen oxidase gene

  • H.-M. Lam
  • Laryssa Dragan
  • H. C. Tsou
  • Hans Merk
  • Monica Peacocke
  • Günter Goerz
  • Shigeru Sassa
  • Maureen Poh-Fitzpatrick
  • David R. Bickers
  • A. M. Christiano
Original investigation

Abstract

The porphyrias are disorders that result from the inherited or acquired dysregulation of one of the eight enzymes in the heme biosynthetic pathway. Variegate porphyria (VP) is characterized by deficiencies in protoporphyrinogen oxidase (PPO) and has recently been genetically linked (Z = 6.62) to the PPO gene on chromosome 1q21. In this study, we have identified two sequence variants in the PPO gene in a family with VP. The first is a neutral polymorphism at the -47 position of intron 2; this polymorphism is present in the general population and is unlikely to underlie the VP phenotype. The second is a mutation in the PPO gene in a patient with VP; the mutation consists of an apparently de novo 2-bp insertion in exon 3 of PPO and results in a frameshift and downstream premature termination codon. These data establish that a frameshift mutation in PPO is the underlying mutation in this patient with VP and explain the sporadic occurrence of the phenotype in this family.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • H.-M. Lam
    • 1
  • Laryssa Dragan
    • 1
  • H. C. Tsou
    • 1
  • Hans Merk
    • 2
  • Monica Peacocke
    • 1
  • Günter Goerz
    • 3
  • Shigeru Sassa
    • 4
  • Maureen Poh-Fitzpatrick
    • 1
  • David R. Bickers
    • 1
  • A. M. Christiano
    • 1
  1. 1.Department of Dermatology, Columbia University, College of Physicians and Surgeons, 630 West 168th StreetVC-1526, New York, NY 10032, USA Tel.: +1-212-305-9565; Fax: +1-212-305-7391; e-mail: amc65@columbia.eduUS
  2. 2.Department of Dermatology, University Hospital, RWTH Aachen, Aachen, GermanyDE
  3. 3.Department of Dermatology, Heinrich Heine University, Düsseldorf, GermanyDE
  4. 4.The Rockefeller University Hospital, New York, USAUS

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