Clinical Findings and Genetic Analysis of Nine Mexican Families with Bartter Syndrome
Por:
Hernández N.E.G., Pérez L.I.E., Aguilera, Dora, Camargo-Muniz, Maria Dolores, Espinosa C.F.C., Jaramillo M.D.L.C.R., Salvador, Carolina, Gonzalez, Zinaeli Lopez, Hureaux, Marguerite, Vargas-Poussou, Rosa
Publicada:
1 ene 2023
Categoría:
Medicine (miscellaneous)
Resumen:
Background: 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. Aim: Clinical and genetic analysis of families with Antenatal Bartter syndrome (ABS) and with Classic Bartter syndrome (CBS). Methods: 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. Results: 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. Conclusions: 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. © 2023
Filiaciones:
Hernández N.E.G.:
Pediatric Nephrology Service, General Hospital of the National Medical Center, La Raza, Instituto Mexicano del Seguro Social, Mexico City, Mexico
Pérez L.I.E.:
Physiology Department of the Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico
Aguilera, Dora:
Pediatric Nephrology Service, General Hospital of the National Medical Center, La Raza, Instituto Mexicano del Seguro Social, Mexico City, Mexico
Natl Med Ctr, Gen Hosp, Pediat Nephrol Serv, Inst Mexicano Seguro Social, Mexico City, Mexico
Camargo-Muniz, Maria Dolores:
Department of Pediatrics, Northeast National Medical Center, High Specialty Medical Unit No. 25, Instituto Mexicano del Seguro Social, Monterrey, N.L., Mexico
Northeast Natl Med Ctr, Dept Pediat, High Specialty Med Unit 25, Inst Mexicano Seguro Social, Monterrey, NL, Mexico
Espinosa C.F.C.:
General Hospital No. 33, Bahía de Banderas, Nayarit, Mexico
Jaramillo M.D.L.C.R.:
Pediatrics Service, Hospital General León y Colegio de Pediatras, Guanajuato, Mexico
Salvador, Carolina:
Physiology Department of the Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Sch Med, Dept Physiol, Mexico City, Mexico
Gonzalez, Zinaeli Lopez:
Physiology Department of the Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Sch Med, Dept Physiol, Mexico City, Mexico
Hureaux, Marguerite:
Department of Genetics, Hôpital Européen Georges Pompidou Paris, France
Hop Europeen Georges Pompidou Paris, Dept Genet, Paris, France
Vargas-Poussou, Rosa:
Department of Genetics, Hôpital Européen Georges Pompidou Paris, France
Hop Europeen Georges Pompidou Paris, Dept Genet, Paris, France
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Mexico City, Mexico
Gen Hosp 33, Tepic, Nayarit, Mexico
Hosp Gen Leon, Pediat Serv, Guanajuato, Mexico
Colegio Pediat, Guanajuato, Mexico
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