Pediatric Nephrology Service, General Hospital of the National Medical Center, La Raza, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Department of Physiology of the School of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Arch Med Res. 2023 Sep;54(6):102859. doi: 10.1016/j.arcmed.2023.102859. Epub 2023 Jul 27.
Bartter's syndrome (BS) is a group of salt-wasting tubulopathies characterized by hypokalemia, metabolic alkalosis, hypercalciuria, secondary hyperaldosteronism, and low or normal blood pressure. Loss-of-function variants in genes encoding for five proteins expressed in the thick ascending limb of Henle in the nephron, produced different genetic types of BS.
Clinical and genetic analysis of families with Antenatal Bartter syndrome (ABS) and with Classic Bartter syndrome (CBS).
Nine patients from unrelated non-consanguineous Mexican families were studied. Massive parallel sequencing of a gene panel or whole-exome sequencing was used to identify the causative gene.
Proband 1 was homozygous for the pathogenic variant p.Arg302Gln in the SLC12A1 gene encoding for the sodium-potassium-chloride NKCC2 cotransporter. Proband 3 was homozygous for the nonsense variant p.Cys308* in the KCNJ1 gene encoding for the ROMK potassium channel. Probands 7, 8, and 9 showed variants in the CLCKNB gene encoding the chloride channel ClC-Kb: proband 7 was compound heterozygous for the deletion of the entire gene and the missense change p.Arg438Cys; proband 8 presented a homozygous deletion of the whole gene and proband 9 was homozygous for the nonsense mutation p.Arg595*. A heterozygous variant of unknown significance was detected in the SLC12A1 gene in proband 2, and no variants were found in SLC12A1, KCNJ1, BSND, CLCNKA, CLCNKB, and MAGED2 genes in probands 4, 5, and 6.
Genetic analysis identified loss-of-function variants in the SLC12A1, KCNJ1, and CLCNKB genes in four patients with ABS and in the CLCNKB gene in two patients with CBS.
巴特氏综合征（BS）是一组盐耗竭性管状病变，其特征为低钾血症、代谢性碱中毒、高钙尿症、继发性醛固酮增多症以及低血压或正常血压。在肾单位的亨利氏升支粗段表达的五种蛋白的编码基因中的功能丧失变体导致了不同遗传类型的 BS。
对产前巴特氏综合征（ABS）和经典巴特氏综合征（CBS）患者的家族进行临床和遗传分析。
研究了 9 名来自非近亲墨西哥无关家庭的患者。对基因panel 或全外显子组测序进行大规模平行测序，以鉴定致病基因。
先证者 1 为编码钠-钾-氯 NKCC2 共转运体的 SLC12A1 基因纯合致病性变异 p.Arg302Gln。先证者 3 为编码 ROMK 钾通道的 KCNJ1 基因纯合无义变异 p.Cys308*。先证者 7、8 和 9 显示 CLCKNB 基因编码氯离子通道 ClC-Kb 的变异：先证者 7 为整个基因缺失和错义变化 p.Arg438Cys 的复合杂合子；先证者 8 呈现整个基因缺失纯合子，先证者 9 为无义突变 p.Arg595*纯合子。先证者 2 的 SLC12A1 基因检测到一个杂合意义不明的变体，先证者 4、5 和 6 的 SLC12A1、KCNJ1、BSND、CLCNKA、CLCNKB 和 MAGED2 基因均未发现变异。
基因分析在 4 名 ABS 患者和 2 名 CBS 患者的 SLC12A1、KCNJ1 和 CLCNKB 基因中发现了功能丧失变异。
