Searching for mutations in the HNF1B gene in a Brazilian cohort with renal cysts and hyperglycemia

ABSTRACT Objective To verify the presence of variants in HNF1B in a sample of the Brazilian population selected according to the presence of renal cysts associated with hyperglycemia. Subjects and methods We evaluated 28 unrelated patients with clinical suspicion of HNF1B mutation because of the concomitant presence of diabetes mellitus (DM) or prediabetes and renal cysts. Genotyping was accomplished using Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). In positive cases, available relatives were recruited. Results We found two patients with HNF1B mutations. The first presented the variant p.Pro328Leufs*48(c.983delC) and had DM, renal cysts, and hypomagnesemia. The second presented a heterozygous whole gene deletion in HNF1B, DM, renal cysts, body and tail pancreatic agenesis, and hypomagnesemia; this alteration was also found in his two siblings and his father. Conclusion The recruitment of suspected cases of HNF1B gene mutations in Brazilians due to hyperglycemia and renal cysts presents two positive cases. Our cases contribute to the annotation of clinical and biochemical phenotypes of this rare form of maturity-onset diabetes of the young (MODY).

摘要 研究目的：验证在根据高血糖合并肾囊肿筛选的巴西人群样本中，是否存在肝细胞核因子1β（HNF1B）基因变异。研究对象与方法：纳入28名因同时存在糖尿病（DM）或糖尿病前期与肾囊肿而临床疑似HNF1B突变的无亲缘关系患者。采用桑格测序（Sanger sequencing）或多重连接依赖探针扩增（MLPA）进行基因分型。对于检测结果为阳性的病例，招募其可联系到的亲属参与研究。研究结果：共检出2例携带HNF1B突变的患者。首例患者携带变异p.Pro328Leufs*48(c.983delC)，临床表现为糖尿病、肾囊肿与低镁血症。第二例患者为HNF1B基因杂合性全基因缺失，临床表现为糖尿病、肾囊肿、胰腺体尾部发育不全及低镁血症；该变异同时存在于其两名同胞与父亲体内。研究结论：针对巴西高血糖合并肾囊肿的疑似HNF1B基因突变病例进行招募，共检出2例阳性病例。本研究病例有助于补充注释这种罕见青少年发病的成年型糖尿病（MODY）的临床与生化表型。