Assessment of genetic variation(s) in BBS10, BBS6, and BBS12 in a family from Sindh, Pakistan diagnosed with Bardet-Biedl Syndrome.

This study looked at a Pakistani family where 8 people had Bardet-Biedl Syndrome (BBS) to understand which genetic changes might be causing their condition. The researchers examined three specific genes (BBS10, BBS6, and BBS12) that are known to be linked to BBS, comparing the DNA of affected family members to healthy relatives. The researchers found that all 8 people with BBS had the typical symptoms: obesity (especially around the middle), extra fingers or toes, learning difficulties, kidney problems, trouble with smell, breathing infections, and difficulty swallowing. When they looked at the genes, they discovered something interesting - some genetic variations that are commonly reported to cause BBS in other populations were NOT present in this family. Instead, they found different genetic variations in the BBS6, BBS10, and BBS12 genes that seemed to be linked to the condition in this particular family. This research is important because it shows that BBS can be caused by different genetic variations in different populations around the world. This means that genetic testing for BBS might need to be tailored for different ethnic groups, and it could help doctors better understand and diagnose the condition in families from Pakistan and similar populations. While this doesn't lead to immediate treatments, it's an important step toward more personalized genetic testing and potentially better care for families affected by BBS.

To analyse the symptoms of Bardet-Biedl Syndrome, and to check the association of BBS10 (Bardet-Biedl syndrome 10 gene), BBS6 (Bardet-Biedl syndrome 6 gene) and BBS12 (Bardet-Biedl syndrome 12 gene) with the pathogenesis of Bardet-Biedl Syndrome. The case-control study was conducted in Karachi in 2019-20, and comprised Bardet-Biedl Syndrome patients and healthy controls from the same family. Blood was drawn from all the subjects for deoxyribonucleic acid extraction. Genotyping was performed by conventional and tetra primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) to identify the possible genetic variations. To validate the results, samples were randomly selected and sent for sequencing. Data was analysed using SPSS 20, while sequencing data was analysed using the Molecular Evolutionary Genetics Analysis X software. Of the 20 subjects with mean age 15.8+/-5.09 years (range: 9-25 years), 8(40%) were cases and 12(60%) were controls. The male-to-female ratio was 1:1. Pedigree analysis revealed that the pattern of inheritance was autosomal recessive. All the 8(100%) cases were obese compared to the controls. Truncal obesity, polydactyly, learning impairment and dysmorphic features, renal pain, olfactory dysfunction, respiratory tract infection and dysphasia were observed in all the 8(100%) cases. The globally reported genetic variants of BBS10 (rs1057516628 and rs1489342987) and BBS12 (rs121918327 and rs587777802) did not indicate any association with the clinical phenotype in the family concerned. The genetic variations of BBS6 (rs1547, rs1545 and rs1351192494), BBS12 (rs309370, rs2292493) and a BBS10 variant (rs35676114) had significant association with the disease. The genetic variations showed confounding effects of BBS10, BBS6 and BBS12 genes which might indicate the epistatic effects of other variants present on different loci.