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.
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.
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Authors: Shazia Adalat; Adrian S Woolf; Karen A Johnstone; Andrea Wirsing; Lorna W Harries; David A Long; Raoul C Hennekam; Sarah E Ledermann; Lesley Rees; William van't Hoff; Stephen D Marks; Richard S Trompeter; Kjell Tullus; Paul J Winyard; Janette Cansick; Imran Mushtaq; Harjeeta K Dhillon; Coralie Bingham; Emma L Edghill; Rukshana Shroff; Horia Stanescu; Gerhart U Ryffel; Sian Ellard; Detlef Bockenhauer Journal: J Am Soc Nephrol Date: 2009-04-23 Impact factor: 10.121
Authors: Sheila Unger; Maria W Górna; Antony Le Béchec; Sonia Do Vale-Pereira; Maria Francesca Bedeschi; Stefan Geiberger; Giedre Grigelioniene; Eva Horemuzova; Faustina Lalatta; Ekkehart Lausch; Cinzia Magnani; Sheela Nampoothiri; Gen Nishimura; Duccio Petrella; Francisca Rojas-Ringeling; Akari Utsunomiya; Bernhard Zabel; Sylvain Pradervand; Keith Harshman; Belinda Campos-Xavier; Luisa Bonafé; Giulio Superti-Furga; Brian Stevenson; Andrea Superti-Furga Journal: Am J Hum Genet Date: 2013-05-16 Impact factor: 11.025