title: A novel FN1 variant associated with familial hematuria: TBMN?
abstract: OBJECTIVE
  Thin basement membrane nephropathy (TBMN), an autosomal dominant inherited condition in general, is characterized clinically by persistent hematuria and pathologically by thinning of glomerular basement membrane. TBMN is occasionally accompanied with proteinuria, hypertension and renal impairment in some cases. The aim of this study is to explore the genetic defect in a Chinese pedigree with familial hematuria.
  
  
  METHODS
  A four-generation Chinese Han pedigree with familial hematuria was recruited. Exome sequencing was conducted in the proband diagnosed as TBMN, followed by verification in the proband and other family members with Sanger sequencing.
  
  
  RESULTS
  A novel missense variant, c.4616C>G (p.S1539C), in the fibronectin 1 gene (FN1), was identified, and it co-segregated with the disease condition in the family. It was not observed in 100 normal controls.
  
  
  CONCLUSIONS
  A missense variant in the FN1 gene is possibly responsible for familial hematuria or TBMN in this family, which may broaden the phenotype and mutation spectrums of the FN1 gene. A male patient in this family progressed to end-stage renal disease requiring kidney transplantation, supporting that familial hematuria or TBMN may not always be as benign as generally thought. The findings may have new implications for clinical monitoring and genetic counseling of the family, and may also help understand the pathogenesis.
authors.affiliation: Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Lamei
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Deng
authors.affiliation: Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China. Electronic address: hdeng008@yahoo.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Deng
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005353:Fibronectins / Q000235:genetics*; D006417:Hematuria / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis
chemical_list: C067625:FN1 protein, human; D005353:Fibronectins
keywords: Exome sequencing; Familial hematuria; Genetic counseling; Missense variant; The FN1 gene; Thin basement membrane nephropathy