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Clinical and molecular characterisation of Bardet–Biedl syndrome in consanguineous populations: the power of homozygosity mapping
  1. L Abu Safieh1,
  2. M A Aldahmesh1,
  3. H Shamseldin1,
  4. M Hashem1,
  5. R Shaheen1,
  6. H Alkuraya2,
  7. S A F Al Hazzaa3,
  8. A Al-Rajhi2,
  9. F S Alkuraya1,4,5
  1. 1Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  2. 2Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
  3. 3Department of Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  4. 4Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia
  5. 5Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
  1. Correspondence to Fowzan S Alkuraya, Department of Genetics, King Faisal Specialist Hospital and Research Center, MBC 03, PO Box 3354, Riyadh 11211, Saudi Arabia; falkuraya{at}kfshrc.edu.sa

Abstract

Bardet–Biedl syndrome (BBS) is a ciliopathy with pleiotropic effect that manifests primarily as renal insufficiency, polydactyly, retinal dystrophy and obesity. The current phenotype–genotype correlation is insufficient to predict the likely causative mutation that makes sequencing of all 14 BBS genes an often necessary but highly complicated way to identify the underlying genetic defect in affected patients. In this study, homozygosity mapping is shown as a robust approach that is highly suited for genetically heterogeneous autosomal recessive disorders in populations in which consanguinity is prevalent. This approach allowed us to quickly identify seven novel mutations in seven families with BBS. Some of these mutations would have been missed by unguided routine sequencing, which suggests that missed mutations in known BBS genes could be more common than previously thought. This study, the largest to date on Saudi BBS families, also revealed interesting phenotypic aspects of BBS, including the first report of non-syndromic retinitis pigmentosa as a novel BBS phenotype.

  • BBS3
  • retinitis pigmentosa
  • splice-site mutation, genetics
  • clinical genetics
  • molecular genetics
  • ophthalmology

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Footnotes

  • Funding King Faisal Specialist Hospital and Research Center.

  • Competing interests None to declare.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the King Faisal Specialist Hospital and Research Center.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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