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BBS10 mutations are common in ‘Meckel’-type cystic kidneys
  1. Audrey Putoux1,
  2. Soumaya Mougou-Zerelli1,2,3,
  3. Sophie Thomas1,
  4. Nadia Elkhartoufi4,
  5. Sophie Audollent4,
  6. Martine Le Merrer1,
  7. Augusta Lachmeijer5,
  8. Sabine Sigaudy6,
  9. Annie Buenerd7,
  10. Carla Fernandez8,
  11. Anne-Lise Delezoide9,10,
  12. Marie-Claire Gubler11,
  13. Rémi Salomon2,11,
  14. Ali Saad3,
  15. Marie-Pierre Cordier12,
  16. Michel Vekemans1,2,4,
  17. Raymonde Bouvier7,
  18. Tania Attie-Bitach1,2,4
  1. 1INSERM U-781, Hôpital Necker-Enfants Malades, Paris, France
  2. 2Université René Descartes, Paris 5, France
  3. 3Service de Cytogénétique, Génétique Moléculaire et Biologie de la Reproduction, Hôpital Farhat Hached, Sousse, Tunisie
  4. 4Département de Génétique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
  5. 5Department of Clinical Genetics, VU University Medical Center, Amsterdam, Netherlands
  6. 6Département de Génétique Médicale, Unité de Génétique Clinique, C.H.U. de la Timone, Marseille, France
  7. 7Centre de Pathologie Est, CHU de Lyon, Bron, France
  8. 8Service d'Anatomopathologie et de Neuropathologie, C.H.U. de la Timone, Marseille, France
  9. 9Service de Biologie du Développement, Hôpital Robert Debré, AP-HP, Paris, France
  10. 10Faculté de Médecine Paris Diderot, Paris, France
  11. 11INSERM U-574, Hôpital Necker-Enfants Malades, Paris, France
  12. 12Service de Génétique, CHU de Lyon, HFME, Bron, France
  1. Correspondence to Dr Tania Attie-Bitach, Département de Génétique et Unité, INSERM U-781, Hôpital Necker-Enfants Malades, Paris, France; tania.attie{at}inserm.fr

Abstract

Background Bardet–Biedl syndrome (BBS) is a genetically heterogeneous, multisystemic disorder characterised by progressive retinal dystrophy, obesity, hypogenitalism, learning difficulties, renal abnormalities and postaxial polydactyly, with only the last two antenatally observable. BBS is inherited as an autosomal recessive disorder, and 14 genes have been identified to date (BBS1–BBS14). In addition, a complex digenic inheritance has been established in some families. Mutations of the BBS10 gene on chromosome 12q21.2 account for 20% of BBS cases.

Methods Given the fact that mutations in BBS genes have already been found in Meckel-like fetuses, and in light of the major contribution of BBS10 to BBS, the BBS10 gene was sequenced in 20 fetal cases and a child diagnosed antenatally presenting with characteristic renal anomalies and polydactyly, but without biliary dysgenesis.

Results Recessive mutations were identified at the BBS10 locus in five cases: four fetuses and a child. Interestingly, one of them had situs ambiguus, a rare feature in BBS. In the child, BBS gene screening identified a heterozygous BBS6 nonsense mutation in addition to the homozygous BBS10 mutation, in accordance with the suggested multigenic inheritance of the disease.

Conclusions These results confirm that BBS is underdiagnosed antenatally and should systematically be suspected in fetuses with severe cystic kidneys leading to oligoamnios and fetal or perinatal death. Moreover, this study confirms the high frequency of BBS10 mutations, particularly of the p.Cys91LeufsX5 allele, including severe lethal cases.

  • Bardet-Biedl syndrome
  • cystic kidney
  • BBS10
  • ciliopathy
  • genetic screening
  • molecular genetics
  • obstetrics and gynaecology
  • renal medicine
  • genetic screening/counselling
  • Received 1 April 2010
  • Revised 19 May 2010
  • Accepted 7 June 2010

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Footnotes

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Necker Hospital ethics committee.

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

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