A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Clinical Genetics Année : 2021

A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome

Elsa Nourisson
  • Fonction : Auteur
  • PersonId : 948823
Joakim Klar
  • Fonction : Auteur
Niklas Dahl
  • Fonction : Auteur
  • PersonId : 837630
Richard Redon

Résumé

Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinitis pigmentosa, obesity, polydactyly, cognitive impairment and renal failure. Pathogenic variants in 24 genes account for the molecular basis of >80% of cases. Toward saturated discovery of the mutational basis of the disorder, we carefully explored our cohorts and identified a hominid-specific SINE-R/VNTR/Alu type F (SVA-F) insertion in exon 13 of BBS1 in eight families. In six families, the repeat insertion was found in trans with c.1169 T > G, p.Met390Arg and in two families the insertion was found in addition to other recessive BBS loci. Whole genome sequencing, de novo assembly and SNP array analysis were performed to characterize the genomic event. This insertion is extremely rare in the general population (found in 8 alleles of 8 BBS cases but not in >10 800 control individuals from gnomAD-SV) and due to a founder effect. Its 2435 bp sequence contains hallmarks of LINE1 mediated retrotransposition. Functional studies with patient-derived cell lines confirmed that the BBS1 SVA-F is deleterious as evidenced by a significant depletion of both mRNA and protein levels. Such findings highlight the importance of dedicated bioinformatics pipelines to identify all types of variation.
Fichier principal
Vignette du fichier
Delvallée-2020-A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome.pdf (4.2 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03007093 , version 1 (18-12-2020)

Identifiants

Citer

Clarisse Delvallée, Samuel Nicaise, Manuela Antin, Anne-Sophie Leuvrey, Elsa Nourisson, et al.. A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome. Clinical Genetics, 2021, 99 (2), pp.318-324. ⟨10.1111/cge.13878⟩. ⟨hal-03007093⟩
155 Consultations
43 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More