A nonsense mutation in the cytochrome P450 CYP2D6 gene identified in a Caucasian with an enzyme deficiency

Broly, Franck; Marez, Delphine; Guidice, J.‐M. Lo; Sabbagh, N; Legrand, M.; Boone, Philip M.; Meyer, Ursina

doi:10.1007/bf00197419

Cited by 23 publications

(5 citation statements)

References 18 publications

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“…Deficiencies of members of other enzyme families have been described in humans. These include deletion or lack of expression of the cytochrome P450 (CYP) family genes CYP2A6*4, CYP2D6*5, CYP2D6*8, and CYP2C19*4, which metabolize foreign chemicals as well as endogenous steroids (48)(49)(50)(51), and deletion of the glutathione S-transferase (GST) T1 and GSTM1 genes, which belong to the GST gene family that detoxify mutagenic hydrophobic and electrophilic compounds (52,53). Deletions of GSTT1 and GSTM1 are especially common, occurring in 38 and 50% of individuals, respectively, and these proteins share only 55% amino acid identity.…”

Section: Discussionmentioning

confidence: 99%

A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion

Murata

Warren

Riddell

2003

The Journal of Experimental Medicine

183

155

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Minor histocompatibility antigens (minor H antigens) are targets of graft-versus-host disease and graft-versus-leukemia responses after allogeneic human leukocyte antigen identical hematopoietic stem cell transplantation. Only a few human minor H antigens have been molecularly characterized and in all cases, amino acid differences between homologous donor and recipient proteins due to nucleotide polymorphisms in the respective genes were responsible for immunogenicity. Here, we have used cDNA expression cloning to identify a novel human minor H antigen encoded by UGT2B17, an autosomal gene in the multigene UDP-glycosyltransferase 2 family that is selectively expressed in liver, intestine, and antigen-presenting cells. In contrast to previously defined human minor H antigens, UGT2B17 is immunogenic because of differential expression of the protein in donor and recipient cells as a consequence of a homozygous gene deletion in the donor. Deletion of individual members of large gene families is a common form of genetic variation in the population and our results provide the first evidence that differential protein expression as a consequence of gene deletion is a mechanism for generating minor H antigens in humans.

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Section: Discussionmentioning

confidence: 99%

A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion

Murata

Warren

Riddell

2003

The Journal of Experimental Medicine

183

155

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“…The UM phenotype was speculated to be due to a gene duplication, with up to 13 copies present in some individuals (Lundqvist et al, 1999). Allelic variants of CYP2D6*2 × N (N = 2, 3, (Johansson et al, 1993;Marez et al, 1997) CYP2D6*2×N (N =2, 3, 4, 5 or 13) R296C; S486T; N active genes ↑ (d) (Johansson et al, 1993;Aklillu et al, 1996) CYP2D6*7 H324P None (s) (Evert et al, 1994) CYP2D6*8 G169X None (d, s) (Broly et al, 1995) CYP2D6*9…”

Section: Cyp2d6mentioning

confidence: 94%

Polymorphic metabolism by functional alterations of human cytochrome P450 enzymes

Lee

Kim

2011

Arch. Pharm. Res.

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The study of cytochrome P450 pharmacogenomics is of particular interest because of its promise in the development of rational means to optimize drug therapy with respect to patient's genotype to ensure maximum efficacy with minimal adverse effects. Drug metabolizing P450 enzymes are polymorphic and are the main phase I enzymes responsible for the metabolism of clinical drugs. Therefore, polymorphisms in the P450s have the most impact on the fate of clinical drugs in phase I metabolism since almost 80% of drugs in use today are metabolized by these enzymes. Predictive genotyping for P450 enzymes for a more effective therapy will be routine for specific drugs in the future. In this review, we discuss the current knowledge of polymorphic metabolism by functional alterations in nonsynonymous SNPs of P450 1A2, 2A6, 2C8, 2C9, 2C19, 2D6, and 3A4 enzymes.

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“…The CYP2D6*8 allele is a no function allele characterized by a nonsense variant in exon 3 (NM_000106.6: c.505G>T, p.Gly169Ter, rs5030865, legacy 1758G>T) that results in a nonfunctional protein. 57 This allele also contains the common c.886C>T and c.1457G>C variants. It has been identified in the European and American populations with frequencies of 0.02% and 0.1%, respectively.…”

Section: Cyp2d6*8mentioning

confidence: 99%

Recommendations for Clinical CYP2D6 Genotyping Allele Selection

Pratt

Cavallari

Tredici

et al. 2021

The Journal of Molecular Diagnostics

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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A nonsense mutation in the cytochrome P450 CYP2D6 gene identified in a Caucasian with an enzyme deficiency

Cited by 23 publications

References 18 publications

A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion

A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion

Polymorphic metabolism by functional alterations of human cytochrome P450 enzymes

Recommendations for Clinical CYP2D6 Genotyping Allele Selection

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