BLOC1S5 pathogenic variants cause a new type of Hermansky-Pudlak syndrome.
| hal.structure.identifier | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM] | |
| dc.contributor.author | PENNAMEN, Perrine | |
| dc.contributor.author | LE, Linh | |
| hal.structure.identifier | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM] | |
| dc.contributor.author | TINGAUD-SEQUEIRA, Angele | |
| dc.contributor.author | FIORE, Mathieu | |
| dc.contributor.author | BAUTERS, Anne | |
| dc.contributor.author | VAN DUONG BEATRICE, Nguyen | |
| dc.contributor.author | COSTE, Valentine | |
| dc.contributor.author | BORDET, Jean-Claude | |
| dc.contributor.author | PLAISANT, Claudio | |
| hal.structure.identifier | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM] | |
| dc.contributor.author | DIALLO, Modibo | |
| dc.contributor.author | MICHAUD, Vincent | |
| hal.structure.identifier | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM] | |
| dc.contributor.author | TRIMOUILLE, Aurélien | |
| hal.structure.identifier | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM] | |
| dc.contributor.author | LACOMBE, Didier | |
| dc.contributor.author | LASSEAUX, Eulalie | |
| dc.contributor.author | DELEVOYE, Cedric | |
| dc.contributor.author | PICARD, Fanny Morice | |
| dc.contributor.author | DELOBEL, Bruno | |
| dc.contributor.author | MARKS, Michael S | |
| hal.structure.identifier | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM] | |
| dc.contributor.author | ARVEILER, Benoit | |
| dc.date.accessioned | 2023-01-09T14:12:11Z | |
| dc.date.available | 2023-01-09T14:12:11Z | |
| dc.date.issued | 2020-10-01 | |
| dc.identifier.issn | 1530-0366 | |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/171626 | |
| dc.description.abstractEn | Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, excessive bleeding, and often additional symptoms. Variants in ten different genes have been involved in HPS. However, some patients lack variants in these genes. We aimed to identify new genes involved in nonsyndromic or syndromic forms of albinism. Two hundred thirty albinism patients lacking a molecular diagnosis of albinism were screened for pathogenic variants in candidate genes with known links to pigmentation or HPS pathophysiology. We identified two unrelated patients with distinct homozygous variants of the BLOC1S5 gene. Patients had mild oculocutaneous albinism, moderate bleeding diathesis, platelet aggregation deficit, and a dramatically decreased number of platelet dense granules, all signs compatible with HPS. Functional tests performed on platelets of one patient displayed an absence of the obligate multisubunit complex BLOC-1, showing that the variant disrupts BLOC1S5 function and impairs BLOC-1 assembly. Expression of the patient-derived BLOC1S5 deletion in nonpigmented murine Bloc1s5 melan-mu melanocytes failed to rescue pigmentation, the assembly of a functional BLOC-1 complex, and melanosome cargo trafficking, unlike the wild-type allele. Mutation of BLOC1S5 is disease-causing, and we propose that BLOC1S5 is the gene for a new form of Hermansky-Pudlak syndrome, HPS-11. | |
| dc.subject.en | Alleles | |
| dc.subject.en | Animals | |
| dc.subject.en | Blood Platelets | |
| dc.subject.en | Hermanski-Pudlak Syndrome | |
| dc.subject.en | Humans | |
| dc.subject.en | Mice | |
| dc.subject.en | Mutation | |
| dc.title.en | BLOC1S5 pathogenic variants cause a new type of Hermansky-Pudlak syndrome. | |
| dc.title.alternative | Genet Med | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1038/s41436-020-0867-5 | |
| dc.subject.hal | Sciences du Vivant [q-bio]/Médecine humaine et pathologie | |
| dc.identifier.pubmed | 32565547 | |
| bordeaux.journal | Genetics in Medicine | en_US |
| bordeaux.page | 1613-1622 | |
| bordeaux.volume | 22 | |
| bordeaux.hal.laboratories | Maladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211 | en_US |
| bordeaux.issue | 10 | |
| bordeaux.institution | Université de Bordeaux | |
| bordeaux.institution | INSERM | |
| bordeaux.import.source | pubmed | |
| hal.identifier | hal-03966532 | |
| hal.version | 1 | |
| hal.date.transferred | 2023-02-01T02:32:55Z | |
| hal.export | true | |
| workflow.import.source | pubmed | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Genetics%20in%20Medicine&rft.date=2020-10-01&rft.volume=22&rft.issue=10&rft.spage=1613-1622&rft.epage=1613-1622&rft.eissn=1530-0366&rft.issn=1530-0366&rft.au=PENNAMEN,%20Perrine&LE,%20Linh&TINGAUD-SEQUEIRA,%20Angele&FIORE,%20Mathieu&BAUTERS,%20Anne&rft.genre=article |
Files in this item
| Files | Size | Format | View |
|---|---|---|---|
|
There are no files associated with this item. |
|||