Assignment Clinical Information
Nephrotic syndrome of childhood is a rare kidney disorder which affects ~ 4-8 children per 100,000. It is characterised by swelling known as oedema, which is usually first noticed around the eyes, then in the lower legs and rest of the body, and the loss of protein into the urine due to increased permeability of the glomerular membrane in the kidney. Most children respond to treatment with steroids but approximately 20% of cases are inherited and do not respond to steroid treatment. In steroid resistant nephrotic syndrome, kidney biopsies show nonspecific histologic changes such as minimal change, focal segmental glomerulosclerosis (FSGS), and diffuse mesangial proliferation. The disorder progresses to end-stage renal failure in the first or second decades
Inherited steroid resistant nephrotic syndrome is known to be genetically heterogeneous with multiple previously identified genes.
Review the clinical information below and then analyse the exome data provided with respect to the clinical information.
Justify the rationale for undertaking exome sequencing in this scenario and then analyse the exome data to identify genes which are the potential disease causing candidates. Describe assessment of the candidate genes with regards to their likelihood of causing the condition, and then discuss how relating the exome data back to the phenotype and known molecular basis for the disease provides further evidence in support of pathogenicity.
This male infant was the first child of healthy non-consanguineous parents. He developed oedema aged 6 years of age, with accompanying proteinuria and haematuria. Kidney biopsy showed focal segmental glomerulosclerosis (FSGS), tubulo-interstitial infiltrations and tubular dilation. He did not respond to steroids and a diagnosis of steroid resistant nephrotic syndrome was made. He was treated with a renal transplant aged 12 after developing end stage renal failure.
This individual is the sister of sibling 1. She developed oedema aged 3 years of age, with accompanying proteinuria. Kidney biopsy showed FSGS, and global sclerosis with immature glomeruli. She had echogenic kidneys on ultrasound scan. She was treated with a renal transplant aged 6 after developing end stage renal failure.