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A novel likely pathogenic CLCN5 variant in Dent’s disease by S Hayward; J Norton; L Bownass; C Platt; J. C. Ambrose; P Arumugam; R. Bevers; M. Bleda; F. Boardman-Pretty; C. R. Boustred; H. Brittain; M. A. Brown; M. J. Caulfield; G. C. Chan; A. Giess; J. N. Griffin; A. Hamblin; S. Henderson; T. J. P. Hubbard; R. Jackson; L. J. Jones; D. Kasperaviciute; M. Kayikci; A. Kousathanas; L. Lahnstein; A Lakey; S. E. A. Leigh; I. U. S. Leong; F. J. Lopez; F. Maleady-Crowe; M. McEntagart; F. Minneci; J. Mitchell; L. Moutsianas; M. Mueller; N. Murugaesu; A. C. Need; P. O‘Donovan; C. A. Odhams; C. Patch; D. Perez-Gil; M. B. Pereira; J. Pullinger; T. Rahim; A. Rendon; T. Rogers; K. Savage; K. Sawant; R. H. Scott; A. Siddiq; A. Sieghart; S. C. Smith; A. Sosinsky; A. Stuckey; M. Tanguy; A. L. Taylor Tavares; E. R. A. Thomas; S. R. Thompson; A. Tucci; M. J. Welland; E. Williams; K. Witkowska; S. M. Wood; M. Zarowiecki; H Campbell; E Watson; N Forrester; S Smithson; A Menon; Genomics England Research Consortium is a Medicine article available to read on EtoBox.

## Background The majority of cases of Dent’s disease are caused by pathogenic variants in the __CLCN5__ gene, which encodes a voltage-gated chloride ion channel (ClC-5), resulting in proximal tubular dysfunction. We present three members of the same family and one unrelated paediatric patient with the same insertion-deletion __CLCN5__ variant. The identification of these patients and positive familial segregation led to the re-classification of this variant from one of unknown significance to one of likely pathogenicity. ## Case presentation A 41 year old male presented with end stage kidney failure, proteinuria and haematuria. Whole genome sequencing identified an insertion-deletion variant in __CLCN5__, resulting in a missense change (c.1744\_1745delinsAA p.(Ala582Lys)). His brother and nephew, who both exhibited renal impairment, haematuria, proteinuria, glycosuria and nephrocalcinosis, were found to have the same variant. In addition, genetic testing of an unrelated paediatric patient who presented with proteinuria and hypercalciuria, demonstrated the same variant. ## Conclusions The identification of this novel variant in four individuals with features of Dent’s disease, has

Author

S Hayward; J Norton; L Bownass; C Platt; J. C. Ambrose; P Arumugam; R. Bevers; M. Bleda; F. Boardman-Pretty; C. R. Boustred; H. Brittain; M. A. Brown; M. J. Caulfield; G. C. Chan; A. Giess; J. N. Griffin; A. Hamblin; S. Henderson; T. J. P. Hubbard; R. Jackson; L. J. Jones; D. Kasperaviciute; M. Kayikci; A. Kousathanas; L. Lahnstein; A Lakey; S. E. A. Leigh; I. U. S. Leong; F. J. Lopez; F. Maleady-Crowe; M. McEntagart; F. Minneci; J. Mitchell; L. Moutsianas; M. Mueller; N. Murugaesu; A. C. Need; P. O‘Donovan; C. A. Odhams; C. Patch; D. Perez-Gil; M. B. Pereira; J. Pullinger; T. Rahim; A. Rendon; T. Rogers; K. Savage; K. Sawant; R. H. Scott; A. Siddiq; A. Sieghart; S. C. Smith; A. Sosinsky; A. Stuckey; M. Tanguy; A. L. Taylor Tavares; E. R. A. Thomas; S. R. Thompson; A. Tucci; M. J. Welland; E. Williams; K. Witkowska; S. M. Wood; M. Zarowiecki; H Campbell; E Watson; N Forrester; S Smithson; A Menon; Genomics England Research Consortium

Publisher

Springer Science and Business Media LLC

Published

2023

Field

Medicine (Health Sciences)