5型巴尔得-别德尔综合征1例报告并文献复习

BARDET-BIEDL SYNDROME TYPE 5: A CASE REPORT AND LITERATURE REVIEW

目的探讨5型巴尔得-别德尔综合征(Bardet-Biedl syndrome,BBS)患者的临床特征,尤其是其表型和基因型,以提高临床对该病的认识。方法收集1例BBS成年患者的临床资料,对先证者提取基因组DNA进行全外显子捕获和测序,采用Sanger法对其父母高通量测序检出的致病基因位点进行验证,并进行家系突变分析和文献复习。结果患者,男,31岁,生后发现多指(趾)畸形;自幼肥胖、多尿、多饮伴夜尿;7岁时发现视力低下,20岁时发现肾功能异常。入院进一步检查发现双眼黄斑区视网膜全层萎缩、双肾萎缩伴囊肿性改变,慢性肾脏病5期。基因检测结果显示,BBS 5基因有2个复合杂合变异:c.1A>G(p.Met1?)以及1~5号外显子的大片段缺失变异c.(?-60)(386+1_387-1)del,均为严重致病性变异。结论报道了我国1例BBS 5基因变异的BBS患者,首次发现5型BBS患者有严重的肾脏表型。新发现了2种BBS 5致病性的变异,丰富了人类BBS的基因突变谱。

Objective To investigate the clinical features of Bardet-Biedl syndrome(BBS)type 5,especially its phenotype and genotype,and to improve the awareness of this disease.Methods Related clinical data were collected from an adult patient with BBS.Whole exome capture and sequencing were performed for the genomic DNA of the proband,and Sanger sequencing was used to validate the pathogenic genetic loci detected by high-throughput sequencing in the proband’s parents.A family mutation analysis and a literature review were also performed.Results The male patient,aged 31 years,was born with polydactyly and had obesity,polyuria,polydipsia,and nocturia since childhood.He was found to have poor vision at the age of 7 years and abnormal renal function at the age of 20 years.Further examination after admission showed whole-layer retinal atrophy at the macular area in both eyes,atrophy and cyst-like changes of both kidneys,and stage 5 chronic kidney disease.Genetic testing revealed two compound heterozygous mutations in the BBS5 gene,c.1A>G(p.Met1?)and c.(?-60)_(386+1_387-1)del(large fragment deletion in exon 1-5),both of which were severely pathogenic mutations.Conclusion This article reports a BBS patient with BBS 5 gene mutations in China,and severe renal phenotype is observed for the first time in BBS type 5.Two novel pathogenic mutations of the BBS 5 gene are identified,which have enriched the spectrum of BBS gene mutations.