LAUSR

Background: Bardet-Biedl Syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder with a wide spectrum of clinical features. To date, mutations in 21 different genes (BBS1-21) have been identified as causing isolated or complex BBS phenotypes. In this report, we present three Chinese Miao ethnic patients who were diagnosed with BBS on the basis of characteristic clinical features and investigated the exsome of these patients. Methods: To evaluate disease genes, the Agilent SureSelect system and Illumina HiSeq 2000 platform for whole exome enrichment and sequencing (WES) were used on the proband and her mother. Variants that fit a recessive model of inheritance only were compared and filtered using public databases. Variants detected by exome sequencing were validated by Sanger sequencing. A total of 981 phenotypically normal subjects were enrolled as control data set. Results: A frameshift homozygous germline mutation in BBS7 was detected by WES and identified by Sanger sequencing in affected individuals. This mutation was predicted to result in premature termination of exon5 (c.389_390delAC, p.Asn130ThrfsX3; RefSeq NM_176824.2) and lead to a 133 amino acid truncated protein. The inheritance patterns in the families are consistent with autosomal recessive inheritance, and no such homozygous mutation was found in the other 981 controls. Conclusion: This mutation has not yet been described in any reported literature, and this is the first report on BBS7 mutation in Chinese Miao families with BBS phenotypes.