Here, we show that the BBBsome, a macromolecule composed of eight Bardet-Biedl syndrome (BBS) proteins including BBS1, is a critical determinant of cell migration and wound healing.
We document a female affected with BBS carrying the most common BBS1 mutation (BBS1: Met390Arg) on the maternal allele and an insertion of a ~1.7-kb retrotransposon in exon 13 on the paternal allele.
Here we describe the successful generation of an induced pluripotent stem cell (iPSC) KCi001-A from a BBS patient compound heterozygous for two disease causing BBS1 variants c.1169T>G, p. (Met390Arg)/c.1135G>C, p.(Gly370Arg).Resource table.
Three different fibroblast lines, K40 and K48 from healthy controls and BBS1 from a patient with Bardet-Biedl syndrome, were used in two independent setups.
At least 21 candidate BBS-associated genes (BBS1-19, NPHP1, and IFT172) have previously been identified, and all of them play important roles in ciliary function.
In this study, 15 patients with clinically diagnosed BBS were investigated using a next generation sequencing panel which included 17 known BBS causing genes (BBS1, BBS2, ARL6, BBS4, BBS5, MKKS, BBS7, TTC8, BBS9, BBS10, TRIM32, BBS12, MKS1, NPHP6, WDPCP, SDCCAG8, NPHP1).
Targeted multi-gene panel testing for the diagnosis of Bardet Biedl syndrome: Identification of nine novel mutations across BBS1, BBS2, BBS4, BBS7, BBS9, BBS10 genes.
We provide the first evidence of BBS12 mutations related to severe phenotypes as previously described for patients with BBS10, while BBS1 ocular phenotype should not be considered as mild as generally reported when compared with other BBS phenotypes.
Furthermore, we show that BBS1 with the M390R mutation, responsible for 30% of all reported BBS disease cases, fails to interact with ARL6-GTP, thus providing a molecular rationale for patient pathologies.
Clinical reanalysis indicated co-ocurrence of two different phenotypes in the same family: Bardet-Biedl syndrome in the individual harboring the BBS1 mutation and non-syndromic arRP in extended family members.