Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, Brazil.
Nephron. 2023;147(8):478-495. doi: 10.1159/000528557. Epub 2023 Mar 7.
Genetic testing is recommended for accurate diagnosis of Bartter syndrome (BS) and serves as a basis for implementing specific target therapies. However, populations other than Europeans and North Americans are underrepresented in most databases and there are uncertainties in the genotype-phenotype correlation. We studied Brazilian BS patients, an admixed population with diverse ancestry.
We evaluated the clinical and mutational profile of this cohort and performed a systematic review of BS mutations from worldwide cohorts.
Twenty-two patients were included; Gitelman syndrome was diagnosed in 2 siblings with antenatal BS and congenital chloride diarrhea in 1 girl. BS was confirmed in 19 patients: BS type 1 in 1 boy (antenatal BS); BS type 4a in 1 girl and BS type 4b in 1 girl, both of them with antenatal BS and neurosensorial deafness; BS type 3 (CLCNKB mutations): 16 cases. The deletion of the entire CLCNKB (1-20 del) was the most frequent variant. Patients carrying the 1-20 del presented earlier manifestations than those with other CLCNKB-mutations and the presence of homozygous 1-20 del was correlated with progressive chronic kidney disease. The prevalence of the 1-20 del in this BS Brazilian cohort was similar to that of Chinese cohorts and individuals of African and Middle Eastern descent from other cohorts.
This study expands the genetic spectrum of BS patients with different ethnics, reveals some genotype/phenotype correlations, compares the findings with other cohorts, and provides a systematic review of the literature on the distribution of BS-related variants worldwide.
基因检测对巴腾病（Bartter syndrome，BS）的准确诊断至关重要，也是实施特定靶向治疗的基础。然而，大多数数据库中欧洲裔和北美裔以外的人群代表性不足，且基因型-表型相关性存在不确定性。我们研究了巴西 BS 患者，这是一个具有多种祖先的混合人群。
我们评估了该队列的临床和突变特征，并对来自全球队列的 BS 突变进行了系统评价。
共纳入 22 例患者；2 例同胞在产前诊断为 BS，1 例女孩产前诊断为先天性氯性腹泻，1 例女孩诊断为 Gitelman 综合征。19 例患者确诊为 BS：1 例男孩为 BS 1 型（产前 BS）；1 例女孩为 BS 4a 型，另 1 例女孩为 BS 4b 型，均为产前 BS 伴感音神经性耳聋；16 例为 BS 3 型（CLCNKB 突变）。CLCNKB 全部缺失（1-20 del）是最常见的变异。携带 1-20 del 的患者比携带其他 CLCNKB 突变的患者更早出现症状，且纯合 1-20 del 的存在与进行性慢性肾脏病相关。该巴西 BS 队列中 1-20 del 的患病率与中国队列以及来自其他队列的非洲和中东裔个体相似。
本研究扩展了不同种族 BS 患者的遗传谱，揭示了一些基因型-表型相关性，与其他队列进行了比较，并对全球范围内 BS 相关变异的文献进行了系统评价。
