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      A de novo mutation in KCNN3 associated with autosomal dominant idiopathic non-cirrhotic portal hypertension.

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          Abstract

          Non-cirrhotic portal hypertension is characterized by histopathological abnormalities in the liver, mostly affecting small intrahepatic portal veins that cause portal hypertension in the absence of cirrhosis. It can be secondary to coagulation disorders or toxic agents. However, most cases are idiopathic non-cirrhotic portal hypertension (INCPH) and familial cases are rare. We report a family in which a father and three of his four children conceived with three different mothers are affected by INCPH. Whole exome and Sanger sequencing showed the father to have a de novo single nucleotide substitution c.1348G>C in the KCNN3 gene that was transmitted to all three of his affected offspring. The KCNN3 gene encodes small conductance calcium-activated potassium (SK) channel 3. SK channels are involved in the regulation of arterial and venous vascular tone by causing smooth muscle relaxation on activation. No data exist on the expression and function of SK channels in portal veins. The autosomal dominant inheritance in this unique pedigree and the single de novo mutation identified, strongly suggests that KCNN3 mutations have a pathogenetic role in INCPH.

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          Author and article information

          Journal
          J. Hepatol.
          Journal of hepatology
          Elsevier BV
          1600-0641
          0168-8278
          Apr 2016
          : 64
          : 4
          Affiliations
          [1 ] Department of Pediatric Gastroenterology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
          [2 ] Department of Medical Genetics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
          [3 ] Department of Pathology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
          [4 ] Department of Hepatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
          [5 ] Department of Pediatric Genetics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: j.m.cobben@amc.uva.nl.
          Article
          S0168-8278(15)00785-0
          10.1016/j.jhep.2015.11.027
          26658685
          16181172-badb-4dea-a830-b0ef429e16c3
          History

          Dominant inheritance,Idiopathic non-cirrhotic portal hypertension,KCNN3,Single nucleotide substitution,Small conductance calcium-activated potassium channel,Whole exome sequencing

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