title: Diagnostic strategy for inherited hypomagnesemia.
abstract: BACKGROUND
  Hereditary hypomagnesemia is difficult to diagnose accurately because of its rarity and the variety of causative genes. We established a flowchart for identifying responsible genes for hypomagnesemia, and we confirmed its diagnostic efficacy in patients with suspected inherited hypomagnesemia.
  
  
  METHODS
  We established a flowchart and applied it to five index cases with suspected inherited hypomagnesemia. Direct sequence analysis was used to detect the causative gene variants in four cases, and targeted sequencing analysis using next-generation sequencing (NGS) of all causative genes for hypomagnesemia was used in one.
  
  
  RESULTS
  Expected pathogenic variants were detected in the HNF1B, TRPM6, CLDN16, CASR, or SLC12A3 gene in all five cases. The results of all genetic analyses were consistent with the clinical diagnostic results using the flowchart.
  
  
  CONCLUSIONS
  Accurate genetic diagnosis is crucial for estimating the prognosis, detecting complications in organs other than the kidneys, and for directing genetic counseling. The developed flowchart for identifying responsible genes for hypomagnesemia was useful for diagnosing inherited hypomagnesemia. In addition, NGS analysis will help to resolve clinical difficulties in making an accurate diagnosis and thus improve the diagnostic strategy for inherited hypomagnesemia.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Horinouchi
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan. nozu@med.kobe-u.ac.jp.
authors.forename: Kandai
authors.initials: K
authors.lastname: Nozu
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kamiyoshi
authors.affiliation: Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kamei
authors.affiliation: Department of Pediatrics, Wakayama Medical University, Wakayama, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Togawa
authors.affiliation: Department of Pediatrics, Wakayama Medical University, Wakayama, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shima
authors.affiliation: Department of Nephrology, Komaki City Hospital, Aichi, Japan.
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Urahama
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Yamamura
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Minamikawa
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Nakanishi
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Fujimura
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Morioka
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ninchoji
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaito
authors.affiliation: Department of Pediatrics, Wakayama Medical University, Wakayama, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakanishi
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan.
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D053565:Hypercalciuria / Q000175:diagnosis / Q000235:genetics*; D007223:Infant; D008297:Male; D009397:Nephrocalcinosis / Q000175:diagnosis / Q000235:genetics*; D015499:Renal Tubular Transport, Inborn Errors / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
keywords: Diagnostic flowchart; Hereditary hypomagnesemia; Next-generation sequencing