Spectrum of HNF1B Mutations in a Large Cohort of Patients Who Harbor Renal Diseases
Spectrum of HNF1B Mutations in a Large Cohort of Patients Who Harbor Renal Diseases
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DOI：
10.2215/cjn.06810909
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发表时间：
2010-06-01
影响因子：
9.8
通讯作者：
Salomon, Remi
中科院分区：
文献类型：
--
作者：
Heidet, Laurence;Decramer, Stephane;Salomon, Remi
背景和目的：肝细胞核因子1 β (HNF1 β)是一种对肾脏和胰腺发育至关重要的转录因子。在人类中，HNF1B的突变导致肾脏和尿路的先天性异常、胰腺萎缩、5型青少年的成熟型糖尿病和生殖器畸形。设计、设置、参与者和测量：我们报告了对377例不同肾脏表型（大小不超过+ 3sd的高回声肾、多囊肾病、肾发育不全、肾发育不全、囊性发育不良或与UMOD突变无关的高尿酸血症小管间质肾病）的不相关病例进行FINF1B筛查。结果：在75例（19.9%）指标病例中发现杂合突变，包括42例全基因缺失，1例外显子缺失，32例小突变。18个突变是新的。新星突变占66%的缺失和40%的小突变。在携带HNF1B突变的患者中，我们能够研究产前超声检查（56个先证），在出生前更常见的是大小正常或稍微增强的孤立高回声肾脏（56个中有34个）。其他各种产前肾脏表型与HNF1B突变相关，但频率较低。四名先证者患糖尿病。高尿酸血症和低镁血症，虽然没有系统的调查，但经常是相关的。结论：这一大型系列研究表明，与FINF1B突变相关的肾脏疾病的严重程度变化很大（从产前肾功能衰竭到成年期肾功能正常），与基因型无关。中华临床医学杂志，2010,31(5):1079-1090。doi: 10.2215 / CJN.06810909
Background and objectives: Hepatocyte nuclear factor 1 beta (HNF1 beta) is a transcription factor that is critical for the development of kidney and pancreas. In humans, mutations in HNF1B lead to congenital anomalies of the kidney and urinary tract, pancreas atrophy, and maturity-onset diabetes of the young type 5 and genital malformations.Design, setting, participants, & measurements: We report FINF1B screening in a cohort of 377 unrelated cases with various kidney phenotypes (hyperechogenic kidneys with size not more than +3 SD, multicystic kidney disease, renal agenesis, renal hypoplasia, cystic dysplasia, or hyperuricemic tubulointerstitial nephropathy not associated with UMOD mutation).Results: We found a heterozygous mutation in 75 (19.9%) index cases, consisting of a deletion of the whole gene in 42, deletion of one exon in one, and small mutations in 32. Eighteen mutations were novel. De nova mutations accounted for 66% of deletions and 40% of small mutations. In patients who carried HNF1B mutation and for whom we were able to study prenatal ultrasonography (56 probands), isolated hyperechogenic kidneys with normal or slightly enhanced size were the more frequent (34 of 56) phenotype before birth. Various other prenatal renal phenotypes were associated with HNF1B mutations, at a lesser frequency. Diabetes developed in four probands. Hyperuricemia and hypomagnesemia, although not systematically investigated, were frequently associated.Conclusions: This large series showed that the severity of the renal disease associated with FINF1B mutations was extremely variable (from prenatal renal failure to normal renal function in adulthood) and was not correlated with the genotype. Clin J Am Soc Nephrol 5: 1079-1090, 2010. doi: 10.2215/CJN.06810909