Alterations in the ferrochelatase gene (FECH) are the basis of the phenotypic expressions in erythropoietic protoporphyria. The phenotype is due to the presence of a mutation in the FECH gene associated in trans to the c.315–48 T > C variant in the intron 3. The latter is able to increase the physiological quota of alternative splicing events in the intron 3. Other two variants in the FECH gene (c.1–252A > G and c.68–23C > T) have been found to be associated to the intron 3 variant in some populations and together, they constitute a haplotype (ACT/GTC), but eventually, their role in the alternative splicing event has never been elucidated. The absolute number of the aberrantly spliced FECH mRNA molecules and the absolute expression of the FECH gene were evaluated by digital PCR technique in a comprehensive cohort. The number of splicing events that rose in the presence of the c.315–48 T > C variant, both in the heterozygous and homozygous condition was reported for the first time. Also, the percentage of the inserted FECH mRNA increased, even doubled in the T/C cases, compared to T/T cases. The constant presence of variants in the promoter and intron 2 did not influence or modulate the aberrant splicing. The results of FECH gene expression suggested that the homozygosity for the c.315–48 T > C variant could be considered pathological. Thus, this study identified the homozygotes for the c.315–48 T > C variant as pathological. By extension, when the samples were categorised according to the haplotypes, the GTC haplotype in homozygosis was pathological.

Digital PCR (dPCR) analysis reveals that the homozygous c.315–48T>C variant in the FECH gene might cause erythropoietic protoporphyria (EPP) / V. Brancaleoni, F. Granata, P. Missineo, S. Fustinoni, G. Graziadei, E. Di Pierro. - In: MOLECULAR GENETICS AND METABOLISM. - ISSN 1096-7192. - 124:4(2018 Aug), pp. 287-296. [10.1016/j.ymgme.2018.06.005]

Digital PCR (dPCR) analysis reveals that the homozygous c.315–48T>C variant in the FECH gene might cause erythropoietic protoporphyria (EPP)

V. Brancaleoni
;
F. Granata;P. Missineo;S. Fustinoni;E. Di Pierro
2018

Abstract

Alterations in the ferrochelatase gene (FECH) are the basis of the phenotypic expressions in erythropoietic protoporphyria. The phenotype is due to the presence of a mutation in the FECH gene associated in trans to the c.315–48 T > C variant in the intron 3. The latter is able to increase the physiological quota of alternative splicing events in the intron 3. Other two variants in the FECH gene (c.1–252A > G and c.68–23C > T) have been found to be associated to the intron 3 variant in some populations and together, they constitute a haplotype (ACT/GTC), but eventually, their role in the alternative splicing event has never been elucidated. The absolute number of the aberrantly spliced FECH mRNA molecules and the absolute expression of the FECH gene were evaluated by digital PCR technique in a comprehensive cohort. The number of splicing events that rose in the presence of the c.315–48 T > C variant, both in the heterozygous and homozygous condition was reported for the first time. Also, the percentage of the inserted FECH mRNA increased, even doubled in the T/C cases, compared to T/T cases. The constant presence of variants in the promoter and intron 2 did not influence or modulate the aberrant splicing. The results of FECH gene expression suggested that the homozygosity for the c.315–48 T > C variant could be considered pathological. Thus, this study identified the homozygotes for the c.315–48 T > C variant as pathological. By extension, when the samples were categorised according to the haplotypes, the GTC haplotype in homozygosis was pathological.
c.315-48 T > C; dPCR; EPP; FECH; Endocrinology, Diabetes and Metabolism; Biochemistry; Molecular Biology; Genetics; Endocrinology
Settore MED/09 - Medicina Interna
ago-2018
Article (author)
File in questo prodotto:
File Dimensione Formato  
Brancaleoni_Mol Genet Metab_2018.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.24 MB
Formato Adobe PDF
1.24 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
1-s2.0-S1096719218301938-main.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.24 MB
Formato Adobe PDF
1.24 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/581011
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 4
social impact