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

Clarisse Delvallée, Samuel Nicaise, Manuela Antin, Anne Sophie Leuvrey, Elsa Nourisson, Carmen C. Leitch, Georgios Kellaris, Corinne Stoetzel, Véronique Geoffroy, Sophie Scheidecker, Boris Keren, Christel Depienne, Joakim Klar, Niklas Dahl, Jean François Deleuze, Emmanuelle Génin, Richard Redon, Florence Demurger, Koenraad Devriendt, Michèle Mathieu-DramardChristine Poitou-Bernert, Sylvie Odent, Nicholas Katsanis, Jean Louis Mandel, Erica E. Davis, Hélène Dollfus, Jean Muller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)318-324
Number of pages7
JournalClinical genetics
Issue number2
StatePublished - Feb 2021


  • BBS1
  • Bardet-Biedl syndrome
  • Mobile element insertion
  • SVA F
  • founder effect

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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