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.

Case presentation: 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.

Conclusion: 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.

Keywords: Congenital nephrotic syndrome; Gene mutation; Juvenile nephronophthisis; Next generation sequencing; Pierson syndrome.

Fig. 1

Sequencing of the LAMB2 gene. a DNA sequencing profile showing exon9 c.1176_1178delTCT mutation in LAMB2, which was derived from the patient’s mother. The arrow indicates the position of the mutation. b The intron 29 c.4923 + 2 T > G mutation in LAMB2 was inherited from the patient’s father. The arrow indicates the position of the mutation

Fig. 2

Sequencing of the NPHP1 gene. a DNA sequencing profile showing exon8 c.922 T > C (p.Ser308Pro) in NPHP1, which was derived from the patient’s mother. The arrow indicates the position of the mutation. b The exon 17 c.1757G > A (p.Arg586Gln) mutation in NPHP1 was inherited from the patient’s father. The arrow indicates the position of the mutation