title: Simultaneous mutations of LAMB2 and NPHP1genes in a Chinese girl with isolated congenital nephrotic syndrome: a case report.
abstract: BACKGROUND
  LAMB2 mutations cause Pierson syndrome (OMIM 609049), an autosomal recessive genetic disease typically characterized by congenital nephrotic syndrome (CNS) and early onset renal failure, as well as bilateral microcoria. NPHP1 mutations cause familial juvenile nephronophthisis type 1 (NPHP1, OMIM 256100), another autosomal recessive renal disease that usually occurs years after birth. Both Pierson syndrome and nephronophthisis cause end-stage renal disease and rare kidney diseases in children. We report an extremely rare case of concurrent mutations of LAMB2 and NPHP1 in a Chinese girl with isolated CNS and the association of the phenotype with novel non-truncating mutations of LAMB2.
  
  
  METHODS
  A-34-day-old girl presented with CNS but no eye abnormalities, and mild hyperechogenicity of kidneys. A novel c.1176_1178delTCT mutation caused deletion of a glycine in exon 9 of LAMB2, and another mutation c.4923 + 2 T > G led to a splicing error. In addition, compound heterozygous mutations of NPHP1 were identified in this child using next generation sequencing, and confirmed by Sanger sequencing.
  
  
  CONCLUSIONS
  Mutations of the LAMB2 and NPHP1 are present in infants with isolated CNS. Next generation sequencing enabled high-throughput screening for mutant genes promptly, with clinically significant outcomes. In addition, our results expand the phenotype spectrum of LAMB2 mutations as the only renal manifestation.
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, China.
authors.forename: Liru
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, China. jhzhou@tjh.tjmu.edu.cn.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D002681:China; D003598:Cytoskeletal Proteins; D005260:Female; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007797:Laminin / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D005819:Genetic Markers; D007797:Laminin; D008565:Membrane Proteins; C108725:NPHP1 protein, human; C058783:laminin beta2
keywords: Congenital nephrotic syndrome; Gene mutation; Juvenile nephronophthisis; Next generation sequencing; Pierson syndrome