Novel mutations and phenotypic effect of the splice site modulator ivs3-48c in nine swedish families with erythropoietic protoporphyria

ABSTRACT.  Erythropoietic protoporphyria (EPP) is an inherited disorder, caused by a partial deficiency of ferrochelatase (FECH), the last enzyme of the heme biosynthetic pathway. The

deficiency results in accumulation of protoporphyrin, primarily in erythroid cells, and the major clinical feature is cutaneous photosensitivity. In addition, some patients may develop liver

complications. Several EPP-coupled mutations have been identified in the _FECH_ gene, and the less than 50% of FECH activity seen in patients with overt EPP was recently shown to be due to

the _in trans_ inheritance of one deleterious mutation and a IVS3-48T>C transition in intron 3 of the _FECH_ gene. This IVS3-48T>C transition modulates the use of a constitutive

aberrant splice site, which results in a decreased _FECH_ mRNA level in the carrier. In the present study, the inheritance of four novel (364C>T, 393delC, 532G>A, and 1088-89insGG) and

two previously reported (343C>T and 1001C>T) _FECH_ mutations, and the splice site modulator IVS3-48C was investigated in nine Swedish families with EPP. The methods used for the

_FECH_ gene analysis included denaturating gradient gel electrophoresis, sequencing analysis, and restriction enzyme cleavage. Haplotype analysis, based on the polymorphic loci 287(G/A),

IVS3-48(T/C), and 921(G/A), revealed that all individuals carrying a mutated allele and IVS3-48C _in trans_ to each other were affected by overt EPP. Mild clinical and biochemical EPP signs

may, however, be present in individuals carrying a T at position IVS3-48_ in trans_ to a mutated allele, because this was the case in one of the individuals investigated in the present

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NOVEL ALAS2 MUTATIONS AND THE IMPACT OF X-CHROMOSOME INACTIVATION Article Open access 07 April 2025 ARTICLE PDF AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Porphyria Centre Sweden, C2-71,

Department of Medical Laboratory Sciences and Technology, Division of Clinical Chemistry, Karolinska Institute, Huddinge University Hospital, Stockholm SE-141 86, Sweden. [email protected],

Sweden Å. Wiman, Y. Floderus & P. Harper Authors * Å. Wiman View author publications You can also search for this author inPubMed Google Scholar * Y. Floderus View author publications

You can also search for this author inPubMed Google Scholar * P. Harper View author publications You can also search for this author inPubMed Google Scholar ADDITIONAL INFORMATION Received:

September 9, 2002 / Accepted: November 11, 2002 ACKNOWLEDGMENTS This work was supported by a stipend fund from HemeBiotech A/S, Hillerød, Denmark and by grants from the Swedish Porphyria

Association and the Karolinska Institute. _Correspondence to:_Å. Wiman RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Wiman, Å., Floderus, Y. &

Harper, P. Novel mutations and phenotypic effect of the splice site modulator IVS3-48C in nine Swedish families with erythropoietic protoporphyria. _J Hum Genet_ 48, 70–76 (2003).

https://doi.org/10.1007/s100380300009 Download citation * Published: 01 February 2003 * Issue Date: February 2003 * DOI: https://doi.org/10.1007/s100380300009 SHARE THIS ARTICLE Anyone you

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Springer Nature SharedIt content-sharing initiative * Key words DNA mutational analysis * Heme biosynthesis * Ferrochelatase * FECH mutations * Erythropoietic protoporphyria