A novel founder BBS1 mutation explains a unique high prevalence of Bardet-Biedl syndrome in the Faroe Islands.
OBJECTIVE
Bardet-Biedl syndrome is a multiorgan disease presenting with retinitis pigmentosa leading to blindness. The aim of the study was to investigate the genetic background of Bardet-Biedl syndrome in the Faroe Island. It was hypothesised that a common genetic background for the syndrome would be found.


METHODS
Patients were identified from the files of the Retinitis Pigmentosa Register at the National Eye Clinic, Denmark. The diagnosis of Bardet-Biedl syndrome was verified from medical files. Mutational screening of BBS1, BBS2, BBS4, MKKS and BBS10 was done by denaturing high-performance liquid chromatography.


RESULTS
Out of 13 prevalent cases in the Faroe Islands, 10 patients from nine families were included. A novel splice site mutation in BBS1, c.1091+3G>C, was identified, and this was predicted to affect protein function by skipping 16 amino acids. Nine patients were homozygous for this mutation, while one patient was compound heterozygous with a recurrent BBS1 mutation, p.Met390Arg. The patients presented with severe ophthalmic phenotypes, while the systemic manifestations of the disease were apparently milder.


CONCLUSIONS
A novel BBS1 mutation was identified, most probably a founder mutation, further confirming the Faroe Islands as a genetic isolate. The phenotypic expression of the Faroese patients suggests that different mutations in BBS1 affect various organs differently.
Hjortshøj
T Duelund
TD
Kennedy Center, Gl. Landevej 7, DK-2600 Glostrup, Denmark. tid@kennedy.dk
Grønskov
K
K
Brøndum-Nielsen
K
K
Rosenberg
T
T
D000328:Adult; D017668:Age of Onset; D000368:Aged; D020788:Bardet-Biedl Syndrome / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D003718:Denmark / Q000453:epidemiology; D005260:Female; D018703:Founder Effect; D005654:Fundus Oculi; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D015995:Prevalence; D020033:Protein Isoforms; D011506:Proteins / Q000235:genetics*; D012160:Retina / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
C464790:Bbs1 protein, human; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D011506:Proteins