目的 本文首次报道我国2个巴尔得-别德尔综合征（Bardet-Biedl syndrome，BBS）BBS12基因突变家系，总结患儿的临床特征并分析其家系基因，以提高对该病的认识。 方法 收集两例BBS患儿的临床资料；对基因组DNA进行全外显子捕获和测序，Sanger法对高通量测序结果进行验证，在家系中进行突变分析。 结果 两例患儿均为男性、汉族；生后发现多指（趾）畸形；生后体重迅速增长，因肥胖就诊于内分泌科时发现血肌酐升高，转诊肾内科并确诊。病例1入院进一步检查发现视网膜色素异常、双肾多发囊性占位（慢性肾脏病4期）、房间隔缺损、精神运动发育迟缓、高血压和听力损害，基因检测到尚未报道的BBS12 c.1604T＞G（p.V535G）和BBS12 c.173delA（p.E58Efs*5）复合杂合突变及已知BBS4单杂合错义突变。病例2在胎儿期超声即发现肾多囊性病变，生后因与外界交流少被疑诊“自闭症”，入院查体发现小阴茎、高血压，肾功能损伤达慢性肾脏病3期，基因检测到尚未报道的BBS12 c.1783T＞C（p.W595R）和BBS12 c.1749_1750delA（p.R584Dfs*54）复合杂合突变。两例患儿BBS12基因的2个错义突变位点经生物信息学软件预测为有害突变，经多物种蛋白序列比对，2个突变位点均具有保守性。两例患儿BBS12基因的2个移码突变均造成编码提前终止。 结论 BBS罕见，起病隐匿，可因多指（趾）畸形和肥胖在婴幼儿期首诊，但至今基因确诊病例较少。本文首次报道我国患者BBS12基因突变，该基因型有较严重的肾脏表型。新发现的4种BBS12突变丰富了人类BBS的基因突变谱。

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.