Mutation profile of BBS genes in Iranian patients with Bardet-Biedl syndrome: genetic characterization and report of nine novel mutations in five BBS genes.
Bardet-Biedl syndrome (BBS) is a rare ciliopathy disorder that is clinically and genetically heterogeneous with 18 known genes. This study was performed to characterize responsible genes and mutation spectrum in a cohort of 14 Iranian families with BBS. Sanger sequencing of the most commonly mutated genes (BBS1, BBS2 and BBS10) accounting for ∼50% of BBS patients determined mutations only in BBS2, including three novel mutations. Next, three of the remaining patients were subjected to whole exome sequencing with 96% at 20 × depth of coverage that revealed novel BBS4 mutation. Observation of no mutation in the other patients represents the possible presence of novel genes. Screening of the remaining patients for six other genes (BBS3, BBS4, BBS6, BBS7, BBS9 and BBS12) revealed five novel mutations. This result represents another indication for the genetic heterogeneity of BBS and extends the mutational spectrum of the disease by introducing nine novel mutations in five BBS genes. In conclusion, although BBS1 and BBS10 are among the most commonly mutated genes in other populations like Caucasian, these two seem not to have an important role in Iranian patients. This suggests that a different strategy in molecular genetics diagnostic approaches in Middle Eastern countries such as Iran should be considered.
1] Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran [2] Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
Zohreh
Z
Fattahi
Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
Parvin
P
Rostami
University of California, San Diego, La Jolla, CA, USA.
Amin
A
Najmabadi
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Marzieh
M
Mohseni
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Kimia
K
Kahrizi
1] Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran [2] Women's College Research Institute, Women's College Hospital, Toronto, Canada [3] Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
Mohammad Reza
MR
Akbari
Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
Ariana
A
Kariminejad
1] Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran [2] Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
Hossein
H
Najmabadi
D000595:Amino Acid Sequence; D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D001483:Base Sequence; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D007492:Iran; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D040641:Quantitative Trait Loci; D016415:Sequence Alignment