ABCB6 Polymorphisms are not Overly Represented in Patients with Porphyria Tracking no: ADV-2021-005484R1
Colin Farrell
(1)
,
Gaël Nicolas
(2)
,
Robert Desnick
(3)
,
Charles Parker
(1)
,
Jerome Lamoril
(4)
,
Laurent Gouya
(5)
,
Zoubida Karim
(5)
,
Dimitri Tchernitchko
(6)
,
Brenden Chen
(3)
,
Herve Puy
(7)
,
John Phillips
(1)
1
University of Utah
2 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
3 Mount Sinai School of Medicine
4 Hôpital Louis Mourier - AP-HP [Colombes]
5 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
6 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
7 CRB3 - Centre de recherche biomédicale Bichat-Beaujon
2 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
3 Mount Sinai School of Medicine
4 Hôpital Louis Mourier - AP-HP [Colombes]
5 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
6 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
7 CRB3 - Centre de recherche biomédicale Bichat-Beaujon
Gaël Nicolas
- Fonction : Auteur
- PersonId : 9291
- IdHAL : gael-nicolas
- ORCID : 0000-0002-1671-8274
- IdRef : 08351483X
Jerome Lamoril
- Fonction : Auteur
- PersonId : 816119
- ORCID : 0000-0001-5641-5799
Zoubida Karim
- Fonction : Auteur
- PersonId : 169884
- IdHAL : zoubida-karim
- ORCID : 0000-0002-3724-5592
- IdRef : 174709374
Herve Puy
- Fonction : Auteur
- PersonId : 763317
- ORCID : 0000-0003-3362-2634
- IdRef : 073942170
Résumé
The Mendelian inheritance pattern of acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria is autosomal dominant, but the clinical phenotype is heterogeneous. Within the general population, penetrance is low, but among first-degree relatives of a symptomatic proband, penetrance is higher. These observations suggest that genetic factors, in addition to mutation of the specific enzyme of the biosynthetic pathway of heme, contribute to the clinical phenotype. Recent studies by others suggested that the genotype of the transporter protein ABCB6 contribute to the porphyria phenotype. Identifying the molecule(s) that are transported by ABCB6 has been problematic and has led to uncertainty with respect to how or if variants/mutants contribute to phenotypic heterogeneity. Knockout mouse models of Abcb6 have not provided a direction for investigation as homozygous knockout animals do not have a discrete phenotype. To address the proposed link between ABC6 genotype and porphyria phenotype, a large cohort of patients with acute hepatic porphyria and erythropoietic protoporphyria was analyzed. Our studies showed that ABCB6 genotype did not correlate with disease severity. Therefore, genotyping of ABCB6 in patients with acute hepatic porphyria and erythropoietic protoporphyria is not warranted.
Format du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
ABCB6 Polymorphisms are not Overly Represented in Patients with Porphyria Tracking no: ADV-2021-005484R1
|
Résumé |
en
The Mendelian inheritance pattern of acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria is autosomal dominant, but the clinical phenotype is heterogeneous. Within the general population, penetrance is low, but among first-degree relatives of a symptomatic proband, penetrance is higher. These observations suggest that genetic factors, in addition to mutation of the specific enzyme of the biosynthetic pathway of heme, contribute to the clinical phenotype. Recent studies by others suggested that the genotype of the transporter protein ABCB6 contribute to the porphyria phenotype. Identifying the molecule(s) that are transported by ABCB6 has been problematic and has led to uncertainty with respect to how or if variants/mutants contribute to phenotypic heterogeneity. Knockout mouse models of Abcb6 have not provided a direction for investigation as homozygous knockout animals do not have a discrete phenotype. To address the proposed link between ABC6 genotype and porphyria phenotype, a large cohort of patients with acute hepatic porphyria and erythropoietic protoporphyria was analyzed. Our studies showed that ABCB6 genotype did not correlate with disease severity. Therefore, genotyping of ABCB6 in patients with acute hepatic porphyria and erythropoietic protoporphyria is not warranted.
|
Auteur(s) |
Colin Farrell
1
, Gaël Nicolas
2
, Robert Desnick
3
, Charles Parker
1
, Jerome Lamoril
4
, Laurent Gouya
5
, Zoubida Karim
5
, Dimitri Tchernitchko
6
, Brenden Chen
3
, Herve Puy
7
, John Phillips
1
1
University of Utah
( 300863 )
- 201 Presidents Cir, Salt Lake City, UT 84112
- États-Unis
2
GPMCND -
Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
( 519394 )
- 22, Boulevard Gambetta 76183 Rouen Cedex
- France
3
Mount Sinai School of Medicine
( 227388 )
- États-Unis
4
Hôpital Louis Mourier - AP-HP [Colombes]
( 344348 )
- 178 Rue des Renouillers, 92700 Colombes
- France
5
CRI (UMR_S_1149 / ERL_8252 / U1149) -
Centre de recherche sur l'Inflammation
( 1005007 )
- Faculté de Médecine site Bichat - 16, Rue Henri Huchard - BP 416/4ème étage - 75870 Paris Cedex 18
- France
6
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
( 300156 )
- 46 Rue Henri Huchard, 75018 Paris
- France
7
CRB3 -
Centre de recherche biomédicale Bichat-Beaujon
( 3041 )
- Faculte de Medecine Xavier Bichat 16, Rue Henri Huchard 75870 PARIS CEDEX 18
- France
|
Date de publication électronique |
2021-11-01
|
Date de publication |
2021
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Domaine(s) |
|
DOI | 10.1182/bloodadvances.2021005484 |
Pubmed Id | 34724702 |
Origine :
Fichiers produits par l'(les) auteur(s)
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