title: [Clinical features of the nephrotic syndrome associated with ichthyosis vulgaris and analysis of related gene mutation].
abstract: OBJECTIVE
  To study clinical features of 3 children who presented with nephrotic syndrome (NS) associated with ichthyosis vulgaris (IV), and to detect relationship between NS associated with IV in patients and FLG gene or NPHS2 gene.
  
  
  METHODS
  Clinical and kidney pathological data of the 3 patients were analyzed and progress of pathologic damage in the patient kidney was observed through repeated percutaneous renal biopsy. Using polymerase chain reaction-single strand conformation polymorphism and DNA sequencing, the diversity of the expression of NPHS2 gene in the 3 patients were analyzed, and FLG gene in the 3 patients and parts of their family members with IV was detected.
  
  
  RESULTS
  (1) The age of the 3 patients (patient 1 was a girl and patients 2 and 3 were boys) suffering from NS was 3 years and 8 months, 2 years and 6 months, and 5 years and 3 months, respectively. The age of onset of IV was 1 year and 6 months, 10 months, and 2 years and 6 months, respectively. All the 3 patients were resistant to steroid therapy. Despite multi-immunosuppressive therapy, no clinical response was achieved. The patients were followed up for 1.5 to 4.0 years. The patients displayed continuous proteinuria, renal function was normal, but their heights were lower than other children at the same age. (2) The older brother of patient 1 died of uremia. The other patients' family members did not have kidney disease. (3) Renal histopathology showed that the patients 1 and 2 had mild mesangial proliferative glomerulonephritis (MsPGN) and the patient 3 had minimal change disease (MCD). One and a half years after the first renal biopsy, the patients 1 and 2 underwent repeated renal biopsy. Renal histopathology showed that the 2 patients' disease developed to medium MsPGN. (4) None of the 3 patients had NPHS2 gene mutation. All the three patients had R501X and 2282del4 which are the common gene mutation type of the FLG, and all the patients were heterozygote. With the detection of the FLG gene of the part of the patients of the three families, the second patient's grandfather had the R501X homozygote mutation and the others were the R501X heterozygote mutation and 2282del4 heterozygote mutation.
  
  
  CONCLUSIONS
  The 3 cases of NS associated with IV had no response to steroid and multi-immunosuppressive therapy, the renal damage observed by histopathology progressed fast. The children with NS associated with IV displayed R501X heterozygote mutation and 2282del4 heterozygote mutation of FLG gene, which suggested that the absence of response to steroid and multi-immunosuppressive therapy may be related to the FLG gene.
authors.affiliation: Department of Nephrology, Kidney Laboratory of Hunan Pediatric Research Institute, Hunan Children's Hospital, Changsha 410007, China.
authors.forename: Zhi-hui
authors.initials: ZH
authors.lastname: Li
authors.forename: Tian-hui
authors.initials: TH
authors.lastname: Wu
authors.forename: Cui-rong
authors.initials: CR
authors.lastname: Duan
authors.forename: Mai
authors.initials: M
authors.lastname: Xun
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yin
authors.forename: Li-qiong
authors.initials: LQ
authors.lastname: Zhang
mesh_terms: D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D016112:Ichthyosis Vulgaris / Q000150:complications / Q000235:genetics*; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007668:Kidney / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D009404:Nephrotic Syndrome / Q000150:complications / Q000235:genetics*; D010375:Pedigree
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein