Simultaneous mutations of LAMB2 and NPHP1genes in a Chinese

28 Background: LAMB2 mutations cause Pierson syndrome (OMIM 609049), an 29 autosomal recessive genetic disease typically characterized by congenital nephrotic 30 syndrome (CNS) and early onset renal failure, as well as bilateral microcoria. 31 NPHP1 mutations cause familial juvenile nephronophthisis type 1 (NPHP1, OMIM 32 256100), another autosomal recessive renal disease that usually occurs years after 33 birth. Both Pierson syndrome and nephronophthisis cause end-stage renal disease and 34 rare kidney diseases in children. We report an extremely rare case of concurrent 35 mutations of LAMB2 and NPHP1 in a Chinese girl with isolated CNS and the 36 association of the phenotype with novel non-truncating mutations of LAMB2. 37 Case presentation: A-34-day-old girl presented with CNS but no eye abnormalities, 38 and mild hyperechogenicity of kidneys. A novel c.1176_1178delTCT mutation 39 caused deletion of a glycine in exon 9 of LAMB2, and another mutation c.4923+2T>G 40 led to a splicing error. In addition, compound heterozygous mutations of NPHP1 were 41 identified in this child using next generation sequencing, and confirmed by Sanger 42 sequencing. 43 Conclusion: Mutations of the LAMB2 and NPHP1 are present in infants with isolated 44 CNS. Next generation sequencing enabled high-throughput screening for mutant 45 genes promptly, with clinically significant outcomes. In addition, our results expand 46 the phenotype spectrum of LAMB2 mutations as the only renal manifestation. 47