Mutations in BBS8 gene causes Bardet–Biedl syndrome in two Tunisian families

Abstract

Abstract: : Purpose: To investigate the genes causing BBS in Tunisian families. Methods: A genome wide scan was performed for BBS in 19 Tunisian BBS families. Two point Linkage analyses were performed with the FASTLINK implementation of the MLINK program of the LINKAGE program package. DNA sequencing was performed using ABI BigDye Terminator with an ABI3100 sequencer Results: Two families, 57006 and 57009 showed linkage to the recently described BBS8 locus. Linkage two point analysis in family 57009 using the haplotype for markers D14S280–D14S977–D14S1054 gave a lod score of 3.18 at &#952=0, confirming the linkage to BBS8 locus. Haplotype analysis with family 57006 was also compatible with linkage in the BBS8 locus, although it did not yield a statistically significant lod score by itself. Sequence analysis of the BBS8 gene revealed a homozygous insertion of 16 bp (GGTGGAAGGCCAGGCA) from nucleotides 371 to 387bp of exon 4 in family 57009 and a homozygous substitution in the 5’ (donor) splice site of exon 4 (459+1G→A) in family 57006. Conclusions: This is the first study of the Bardet Bield syndrome in Tunisia. Mutations in the BBS8 gene were seen in 2 of 19 (10.5%) of the Tunisian families. BBS8 is a gene related to BBS4, both having TPR repeats. This suggests the possibility that BBS4 and BBS8 interact within a common pathway.

Keywords: positional cloning • linkage analysis • retina