BBS10 mutations are frequent in “Meckel” type cystic kidneys

Audrey Putoux (1) , Soumaya Mougou-Zerelli (2) , Sophie Thomas (1) , Nadia Elkhartoufi (1) , Sophie Audollent (1) , Martine Le Merrer (1) , Augusta Lachmeijer (3) , Sabine Sigaudy (4) , Annie Buenerd (5) , Carla Fernandez (1) , Anne-Lise Delezoide (6) , Marie-Claire Gubler (1) , Rémi Salomon (1) , Ali Saad (1) , Marie-Pierre Cordier (7) , Michel Vekemans (1) , Raymonde Bouvier (1) , Tania Attié-Bitach (1)

1 Service de néphrologie pédiatrique [CHU Necker]
2 Hôpital Farhat Hached, Sousse
3 VU University Medical Center [Amsterdam]
4 TIMONE - Hôpital de la Timone [CHU - APHM]
5 Centre de Pathologie Est, Lyon
6 Hôpital Robert Debré, Paris
7 HFME - Hôpital Femme Mère Enfant [CHU - HCL]

Background : Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, multisystemic disorder characterized 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, we sequenced the BBS10 gene in 20 fetal cases and a child diagnosed antenatally presenting characteristic renal anomalies and polydactyly, but without biliary dysgenesis. Results: We identified recessive mutations at the BBS10 locus in 5 cases, 4 fetuses and a child. Interestingly, one of them had situs ambiguus, a rare feature in BBS. In the child, BBS genes 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 and particularly of the p.Cys91Leufs*5 allele, including in severe lethal cases.

Mots clés: Genetic screening/counselling; Molecular genetics; Obstetrics and Gynaecology; Renal Medicine

Audrey Putoux, Soumaya Mougou-Zerelli, Sophie Thomas, Nadia Elkhartoufi, Sophie Audollent, et al.. BBS10 mutations are frequent in “Meckel” type cystic kidneys. Journal of Medical Genetics, 2010, 47 (12), pp.848. ⟨10.1136/jmg.2010.079392⟩. ⟨hal-00560780⟩