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Five new mutations in the uroporphyrinogen decarboxylase gene identified in families with cutaneous porphyria.
Blood. 1996 Nov 01; 88(9):3589-600.Blood

Abstract

We describe five new mutations in the uroporphyrinogen decarboxylase (UROD) gene. All mutations were observed in conjunction with decreased erythrocyte UROD and clinical familial porphyria cutanea tarda (fPCT), (four families) or hepatoerythropoietic porphyria (HEP), (one family). The fPCT mutations included three point mutations that resulted in amino acid substitutions: a lysine to glutamine at amino acid position 253 (exon 7); a glycine to arginine at position 318 (exon 10); an isoleucine to threonine at position 334 (exon 10). The lysine to glutamine at amino acid position 253 was found in conjunction with a single C nucleotide deletion in exon 8 on the same allele of the UROD gene in the same family. This deletion resulted in a shift in the reading frame and the introduction of a premature stop codon 8 amino acids downstream. In the fourth family, a 31-bp deletion (nucleotides 828-858: exon 8) of the coding region, resulted in a frameshift and the introduction of a stop codon 19 amino acids downstream. A point mutation was observed in an individual diagnosed with HEP, resulting in an alanine to glycine change at amino acid position 80 and was present on both alleles. All mutations were confirmed in at least one other family member. The impact of these mutations on the function of the UROD protein was examined using in vitro protein expression and with activity assessed using pentacarboxylic acid porphyrinogen I as a substrate for UROD. Although three mutations reduced UROD activity to < 15% of normal, one resulted in a UROD protein with 50% functional activity and the other had near normal activity. These results indicate that many different genetic lesions of the UROD gene are associated with fPCT.

Authors+Show Affiliations

Department of Biochemistry, Royal Melbourne Hospital, Victoria, Australia.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8896428

Citation

McManus, J F., et al. "Five New Mutations in the Uroporphyrinogen Decarboxylase Gene Identified in Families With Cutaneous Porphyria." Blood, vol. 88, no. 9, 1996, pp. 3589-600.
McManus JF, Begley CG, Sassa S, et al. Five new mutations in the uroporphyrinogen decarboxylase gene identified in families with cutaneous porphyria. Blood. 1996;88(9):3589-600.
McManus, J. F., Begley, C. G., Sassa, S., & Ratnaike, S. (1996). Five new mutations in the uroporphyrinogen decarboxylase gene identified in families with cutaneous porphyria. Blood, 88(9), 3589-600.
McManus JF, et al. Five New Mutations in the Uroporphyrinogen Decarboxylase Gene Identified in Families With Cutaneous Porphyria. Blood. 1996 Nov 1;88(9):3589-600. PubMed PMID: 8896428.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Five new mutations in the uroporphyrinogen decarboxylase gene identified in families with cutaneous porphyria. AU - McManus,J F, AU - Begley,C G, AU - Sassa,S, AU - Ratnaike,S, PY - 1996/11/1/pubmed PY - 1996/11/1/medline PY - 1996/11/1/entrez SP - 3589 EP - 600 JF - Blood JO - Blood VL - 88 IS - 9 N2 - We describe five new mutations in the uroporphyrinogen decarboxylase (UROD) gene. All mutations were observed in conjunction with decreased erythrocyte UROD and clinical familial porphyria cutanea tarda (fPCT), (four families) or hepatoerythropoietic porphyria (HEP), (one family). The fPCT mutations included three point mutations that resulted in amino acid substitutions: a lysine to glutamine at amino acid position 253 (exon 7); a glycine to arginine at position 318 (exon 10); an isoleucine to threonine at position 334 (exon 10). The lysine to glutamine at amino acid position 253 was found in conjunction with a single C nucleotide deletion in exon 8 on the same allele of the UROD gene in the same family. This deletion resulted in a shift in the reading frame and the introduction of a premature stop codon 8 amino acids downstream. In the fourth family, a 31-bp deletion (nucleotides 828-858: exon 8) of the coding region, resulted in a frameshift and the introduction of a stop codon 19 amino acids downstream. A point mutation was observed in an individual diagnosed with HEP, resulting in an alanine to glycine change at amino acid position 80 and was present on both alleles. All mutations were confirmed in at least one other family member. The impact of these mutations on the function of the UROD protein was examined using in vitro protein expression and with activity assessed using pentacarboxylic acid porphyrinogen I as a substrate for UROD. Although three mutations reduced UROD activity to < 15% of normal, one resulted in a UROD protein with 50% functional activity and the other had near normal activity. These results indicate that many different genetic lesions of the UROD gene are associated with fPCT. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/8896428/Five_new_mutations_in_the_uroporphyrinogen_decarboxylase_gene_identified_in_families_with_cutaneous_porphyria_ L2 - http://www.diseaseinfosearch.org/result/5879 DB - PRIME DP - Unbound Medicine ER -