Résumé
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 (
BBS
1–8) 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.