Modulation of the phenotype in dominant erythropoietic protoporphyria by a low expression of the normal ferrochelatase allele

Journal Article · Thu Feb 01 04:00:00 EST 1996 · American Journal of Human Genetics

OSTI ID:219859

Gouya, L; Deyback, J C; Lamoril, J ^[1]

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1. Hopital Louis Mourier, Colombes, Paris (France); and others

Erythropoietic protoporphyria (EPP) is a monogenic inherited disorder of the heme biosynthetic pathway due to ferrochelatase (FC) deficiency. EPP is generally considered to be transmitted as an autosomal dominant disease with incomplete penetrance, although autosomal recessive inheritance has been documented at the enzymatic and molecular level in some families. In the dominant form of EPP, statistical analysis of FC activities documented a significantly lower mean value in patients than in asymptomatic carriers, suggesting a more complex mode of inheritance. To account for these findings, we tested a multiallelic inheritance model in one EPP family in which the enzymatic data were compatible with this hypothesis. In this EPP family, the specific FC gene mutation was an exon 10 skipping ({triangle}Ex10), resulting from a G deletion within the exon 10 consensus splice donor site. The segregation of all FC alleles within the family was followed using the {triangle}Ex10 mutation and a new intragenic dimorphism (1520 C/T). mRNAs transcribed from each FC allele were then subjected to relative quantification by a primer extension assay and to absolute quantification by a ribonuclease protection assay. The data support the hypothesis that in this family the EPP phenotype results from the coinheritance of a low output normal FC allele and a mutant {triangle}Ex10 allele. 29 refs, 4 figs., 1 tab.

• OSTI ID: 219859
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 2 Vol. 58; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
DOMINANT MUTATIONS
ENZYME ACTIVITY
ENZYMES
EXONS
GENE MUTATIONS
GENES
GENETICS
HEMIC DISEASES
HEREDITARY DISEASES
MESSENGER-RNA
PATIENTS
PHENOTYPE
SPLICING
STATISTICAL MODELS
TRANSCRIPTION