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      CLCN5 mutation Ser244Leu is associated with X-linked renal failure without X-linked recessive hypophosphatemic rickets.

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          Abstract

          This study demonstrates that a missense mutation in the voltage gated chloride channel, CLCN5, can cause X-linked renal failure without X-linked recessive hypophosphatemic rickets. A large kindred (Family A), initially evaluated in 1974 with an inherited syndrome characterized by hypercalciuria, nephrocalcinosis, low molecular weight proteinuria, renal tubular acidosis, and renal failure, was clinically re-evaluated and genetically characterized. Medical histories, physical examinations, blood chemistries, and 24-hour urine collections were obtained from 48 family members. Both female and male family members exhibited hypercalciuria, nephrolithiasis, and low molecular weight proteinuria. However, only men developed renal insufficiency, consistent with an X-linked recessive gene defect. Genetic linkage located the disease locus on the proximal short arm of the X chromosome (Xp11) where a voltage gated chloride channel gene, CLCN5, had previously been mapped. DNA sequence of the CLCN5 gene demonstrated a missense mutation (Ser244Leu) in affected family members. The same missense mutation has previously been shown to cause X-linked recessive hypophosphatemic rickets. No affected member of Family A had evidence of chronic hypophosphatemia, clinically significant rickets, or osteomalacia. We hypothesize that genetic background, environment, diet, or an unidentified modifying gene may account for the differing phenotypes resulting from this shared gene defect.

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          Author and article information

          Journal
          Kidney Int.
          Kidney international
          Wiley
          0085-2538
          0085-2538
          Jan 1998
          : 53
          : 1
          Affiliations
          [1 ] Division on Aging, Harvard Medical School, Boston, Massachusetts, USA. Kelleher@rascal.med.harvard.edu
          Article
          S0085-2538(15)60360-X
          10.1046/j.1523-1755.1998.00752.x
          9452997
          4c246c8f-3cf0-48b4-8ffc-96500239155b
          History

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