1. ¹Laboratoire de diagnostic génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
2. ²Institut de Génétique et Biologie Cellulaire et Moléculaire, CNRS/INSERM/Université Louis Pasteur, Illkirch, Strasbourg, France
3. ³Hôpitaux Universitaires de Strasbourg, Fédération de Génétique, Strasbourg, France
4. ⁴Service de génétique, Hôpital de la Timone, Marseille, France
5. ⁵Service de Génétique Médicale, CHU de Montpellier, France
6. ⁶Service d'ophtalmologie, CHU de Montpellier, France
7. ⁷Service de Pédiatrie, Centre Hospitalier du Mans, Le Mans, France
8. ⁸Département de Pédiatrie, CHU Amiens, Amiens, France
9. ⁹Service de Génétique, CHU Nancy, France
10. ¹⁰Service de Génétique, CHU Lille, France
11. ¹¹Laboratoire de Génétique Médicale, Hôpital Necker-Enfants Malades, Paris, France
12. ¹²Service de pédiatrie, Hôpital Jean Verdier, Bondy, France
13. ¹³Service de génétique, CHU de Bordeaux, Bordeaux, France
14. ¹⁴Unité de Génétique Clinique, Hôpital Robert Debré, Paris, France
15. ¹⁵Service de Génétique Médicale, CHU d'Angers, Angers, France
16. ¹⁶Centre d'Investigation Clinique des Hôpitaux Universitaires de Strasbourg, Strasbourg, France
17. ¹⁷Direction de la recherche clinique, Hôpitaux Universitaires de Strasbourg, France
18. ¹⁸Collège de France, Paris, France

Correspondence: Professor H Dollfus, Laboratoire de génétique 9ème étage, Faculté de Médecine, 11 rue Humann, 67000 Strasbourg, France. Tel: +33 3 88 12 81 20; Fax: +33 3 88 12 81 25; E-mail: helene.dollfus@medecine.u-strasbg.fr

¹⁹These authors have contributed equally.

Received 21 July 2004; Revised 25 November 2004; Accepted 2 December 2004; Published online 16 March 2005.

Abstract

The phenotype of Bardet–Biedl syndrome (BBS) is defined by the association of retinitis pigmentosa, obesity, polydactyly, hypogenitalism, renal disease and cognitive impairement. The significant genetic heterogeneity of this condition is supported by the identification, to date, of eight genes (BBS1–8) implied with cilia assembly or function. Triallelic inheritance has recently been suggested on the basis of the identification of three mutated alleles in two different genes for the same patient. In a cohort of 27 families, six BBS genes (namely BBS1, BBS2, BBS4, BBS6, BBS7 and BBS8) have been studied. Mutations were identified in 14 families. Two mutations within the same gene have been identified in seven families. BBS1 is most frequently implied with the common M390R substitution at the homozygous state (n=2), or associated with another mutation at BBS1 (n=3). Compound heterozygous mutations have been found in BBS2 (one family) and BBS6 (one family). In seven other families, only one heterozygous mutation has been identified (once in BBS1, twice for BBS2 and three times in BBS6). Although our study did not reveal any families with bona fide mutations in two BBS genes, consistent with a triallelic hypothesis, we have found an excess of heterozygous single mutations. This study underlines the genetic heterogeneity of the BBS and the involvement of possibly unidentified genes.