title: Genetic heterogeneity in patients with Bartter syndrome type 1.
abstract: Bartter syndrome (BS) type 1 is an autosomal recessive kidney disorder caused by loss‑of‑function mutations in the solute carrier family 12 member 1 (SLC12A1) gene. To date, 72 BS type 1 patients harboring SLC12A1 mutations have been documented. Of these 144 alleles studied, 68 different disease‑causing mutations have been detected in 129 alleles, and no mutation was detected in the remaining 15 alleles. The mutation types included missense/nonsense mutations, splicing mutations and small insertions and deletions ranging from 1 to 4 nucleotides. A large deletion encompassing a whole exon in the SLC12A1 gene has not yet been reported. The current study initially identified an undocumented homozygous frameshift mutation (c.1833delT) by Sanger sequencing analysis of a single infant with BS type 1. However, in a subsequent analysis, the mutation was detected only in the father's DNA. Upon further investigation using a next‑generation sequencing approach, a deletion in exons 14 and 15 in both the patient and patient's mother was detected. The deletion was subsequently confirmed by use of a long‑range polymerase chain reaction and was determined to be 3.16 kb in size based on sequencing of the junction fragment. The results of the present study demonstrated that pathogenic variants of SLC12A1 are heterogeneous. Large deletions appear to serve an etiological role in BS type 1, and may be more prevalent than previously thought.
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma, OK 73117, USA.
authors.forename: Mingran
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma, OK 73117, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Ning
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma, OK 73117, USA.
authors.forename: Weihong
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma, OK 73117, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma, OK 73117, USA.
authors.forename: Kaishu
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma, OK 73117, USA.
authors.forename: Wenfu
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Guiying
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma, OK 73117, USA.
authors.forename: Shibo
authors.initials: S
authors.lastname: Li
mesh_terms: D000483:Alleles; D001477:Bartter Syndrome / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D055028:Comparative Genomic Hybridization; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D004252:DNA Mutational Analysis; D005091:Exons; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D064466:Solute Carrier Family 12, Member 1 / Q000235:genetics*
chemical_list: C578714:SLC12A1 protein, human; D064466:Solute Carrier Family 12, Member 1; D004247:DNA