Bascur P M Nicole, Ceballos O M Luisa, Farfán U Mauricio, Gajardo H Iván, López C Joaquín
Hospital Guillermo Grant Benavente, Concepción, Chile.
Hospital Luis Calvo Mackenna, Santiago, Chile.
Rev Chil Pediatr. 2018 Dec;89(6):741-746. doi: 10.4067/S0370-41062018005001204.
Congenital anomalies of the kidney and urinary tract are caused by genetic alterations mostly unknown. Mutations in the gene that codes for hepatocyte nuclear factor 1B (HNF1B) are the most frequently described monogenic causes. Data are unknown in Chile and Latin America.
To determine the presence of variants of the HNF1B gene in Chilean children with conge nital anomalies of the kidney and/or the urinary tract and their clinical characteristics.
Descriptive study with children aged 10 months to 17 years, patients of the Calvo Mackenna Hospital Nephrology Unit, with cystic renal dysplasia, non cystic renal dysplasia/hypoplasia, horses hoe kidney between April and December 2016. HNF1B variants were determined by sequencing of exons 1, 2, 3 and 4 after DNA extraction and amplification. Restriction enzymes were used to define if the variants were homo or heterozygous. Direct family members of index cases were studied with sequencing of the affected exon.
32 patients were included, 43.75% males, median age 11 years. 65.6% of them had non-cystic renal dysplasia, 31.25% cystic renal dysplasia, and 3.15% hor seshoe kidney. In two patients (6.25%) the same heterozygous genetic variant was detected in exon 4, position 1027 (C1027T), not previously described. The study of relatives found the same variant in three out of five individuals, all without congenital nephro-urological anomalies.
We confirmed the presence of a not previously described heterozygous genetic variant of the HNF1B gene. This work initiates the search for this type of mutations in our region which allows us to ap proach the knowledge of causality, determination of extrarenal involvement, and genetic counseling.
肾脏和尿路先天性异常主要由大多未知的基因改变引起。编码肝细胞核因子1B（HNF1B）的基因突变是最常描述的单基因病因。智利和拉丁美洲尚无相关数据。
确定智利患有肾脏和/或尿路先天性异常儿童中HNF1B基因变异的存在情况及其临床特征。
对2016年4月至12月间卡尔沃·麦肯纳医院肾脏病科10个月至17岁患有囊性肾发育不良、非囊性肾发育不良/发育不全、马蹄肾的儿童进行描述性研究。DNA提取和扩增后，通过对第1、2、3和4外显子进行测序来确定HNF1B变异。使用限制性内切酶来确定变异是纯合还是杂合。对索引病例的直系亲属进行受累外显子测序研究。
纳入32例患者，43.75%为男性，中位年龄11岁。其中65.6%患有非囊性肾发育不良，31.25%患有囊性肾发育不良，3.15%患有马蹄肾。在两名患者（6.25%）中，在第4外显子第1027位（C1027T）检测到相同的杂合基因变异，此前未被描述。对亲属的研究发现，五分之三的个体存在相同变异，均无先天性肾泌尿学异常。
我们证实了存在一种此前未被描述的HNF1B基因杂合基因变异。这项工作开启了在我们地区对这类突变的研究，这使我们能够深入了解因果关系、确定肾外受累情况并进行遗传咨询。
