Novel mutations in the BBS12 gene of two Chinese Bardet-Biedl syndrome pedigrees

Abstract

Objective To Summarize and review the clinical data of two Bardet-Biedl syndrome (BBS) children so as to improve our understanding of the disease. Methods Clinical data of two BBS pedigree were collected. Gene analysis was performed by exon capture and next-generation sequencing, validated using Sanger sequencing. Results Both cases were male, Han nationality, born with polydactyly and had rapid weight gain after birth. They went to see the pediatric endocrinologist due to obesity, and found increased serum creatinine level, so were referral to pediatric nephrologists. Case one was further diagnosed rod-cone dystrophy, bilateral renal multiple cysts (chronic kidney disease, stage 4), atrial septal defect, mental retardation, hypertension and abnormal hearing. Two novel heterozygous compound mutation of BBS12 gene [c.1604T>G (p.V535G) paternal, c.173delA (p.E58Efs*5) maternal] and one known BBS4 missense mutation (paternal) were detected. Case two was detected multiple cysts in kidneys by ultrasound in fetal phase. He was suspected to have autism. He had small penis, hypertension and renal injury (chronic kidney disease, stage 3). Two novel heterozygous compound mutation of BBS12 gene [c.1783T>C (p.W595R) paternal, c.1749_1750delA (p.R584Dfs*54) maternal] were detected. All mutations were predicted to be harmful. Conclusions BBS is a rare disease. It is difficult to be diagnosed at early age. Polydactyly and obesity can be the early two symptoms for seeing doctors. Few cases have been diagnosed upon gene analysis. In this study, the mutation of BBS12 in Chinese and 4 novel mutations in BBS12 with severe renal injury are reported for the first time. It will extend the spectrum of BBS gene mutations. Key words: Bardet-Biedl syndrome; Polydactyly; Obesity; BBS12 gene; Chronic kidney disease