Arrayed primer extension technology simplifies mutation detection in Bardet–Biedl and Alström syndrome

Abstract

Bardet-Biedl syndrome (BBS; OMIM no. 209 900) and Alströ m syndrome (ALMS; OMIM no. 203 800) are rare, multisystem genetic disorders showing both a highly variable phenotype and considerable phenotypic overlap; they are included in the emerging group of diseases called ciliopathies. The genetic heterogeneity of BBS with 14 causal genes described to date, serves to further complicate mutational analysis. The development of the BBS-ALMS array which detects known mutations in these genes has allowed us to detect at least one mutation in 40.5% of BBS families and in 26.7% of ALMS families validating this as an efficient and cost-effective first pass screening modality. Furthermore, using this method, we found two BBS families segregating three BBS alleles further supporting oligogenicity or modifier roles for additional mutations. We did not observe more than two mutations in any ALMS family.

Exploring genotype-phenotype relationships in Bardet-Biedl syndrome families

“…Of 37 families included, 2 of them also had an additional mutated allele in another gene: p.(Ala242Ser) ( BBS6 ) in M63 family and p.(His3882Tyr) ( ALMS1 ) in GBB23 family. All these mutations have already been described in the literature 9 24 25…”

“…Molecular analysis of selected patients was previously performed by different approaches 9 24 25. In summary, Bardet-Biedl syndrome/Alström syndrome As per Ophthalmics genotyping microarray (Asper Biotech, Tartu, Estonia), direct sequencing of predominant BBS genes ( BBS1 , BBS10 and BBS12 ) and/or homozygosity mapping (in consanguineous families) were performed in each case.…”

Clinical utility gene card for: Alström Syndrome - update 2013

“…[1][2][3][4][5][6] Several missense alterations of uncertain pathogenicity have been reported. 7 The majority of all mutations are clustered in exon 16 (41%), exon 10 (27%) and exon 8 (25%) of ALMS1.…”

Overview of Bardet–Biedl syndrome in Spain: identification of novel mutations in BBS1,BBS10 and BBS12 genes

“…Our study has relevance in the context of BBS in Spain, as there is few previous data about this syndrome (6,7). The strategy of studying three BBS genes with high contribution in patients previously screened has allowed us to confirm the clinical diagnosis in 16 families (30%).…”