Ongoing Research

Main Research Project:

GENETIC GLOMERULAR DISEASE

There is no age limit for recruited subjects. Adult subjects are welcome. 

 

Inclusion criteria

  • Congenital or infantile nephrotic syndrome with onset in first year of life, OR
  • Steroid-resistant nephrotic syndrome (initial or late steroid resistance) with onset before 25 years of age, OR
  • Persistent subnephrotic proteinuria with likely genetic etiology.

Exclusion criteria

  • Secondary glomerular diseases, such as lupus nephritis, IgA nephropathy, Henoch–Schönlein purpura.
  • Lack of clinical data and histological evidence to track the phenotype.

Procedures required from subjects

Only a single collection of blood or saliva is required and this can be performed during visits to their doctors. Saliva will be collected either by asking the subject to spit into a cup, or by using specific absorbent sponges.

Histological evidence

Availability of histological evidence is important. Primary evidence should be as one of the following forms:

  • Histological slides (preferred)
  • Biopsy in paraffin block (preferred)
  • Renal biopsy samples in formalin (to be pre-arranged)
  • Digital photograph of light microscopy of histology slides
  • Histological evidence may be dated up to 5 years back, as long as it is still clear and undisputable.

Please refer to our protocol for more information on subject recruitment.

Please click here for the protocol.

 

GENETIC CYSTIC RENAL DISEASE

  • Genetic cystic renal diseases

We are exploring the possibility of including genetic cystic disease in our network. There is a possibility of offering genetic sequencing for such cases.

Inclusion criteria

  1. Individuals with ARPKD as defined by
    1. typical findings on renal imaging AND
    2. one or more of the following criteria:
  • Clinical/laboratory signs of hepatic fibrosis
  • Hepatic pathology demonstrating ductal plate abnormality
  • Absence of renal enlargement and/or multiple cysts in both parents
  • Pathoanatomic diagnosis of ARPKD in an affected sibling
  • Family history consistent with autosomal recessive inheritance.
  1. Individuals with nephronophthisis related ciliopathy as defined by
    1. Hyperechogenic kidneys with normal or reduced size and corticomedullary cysts AND one or more of the following extrearenal features
    2. Liver fibrosis
    3. Retinitis pigmentosa or retinal dystrophy/degeneration
    4. Structural brain abnormalities
    5. Polydactyly
    6. Abnormalities of left-right patterning (also known as heterotaxy) eg dextrocardia, situs inversus
  1. Families with isolated nephronophthisis related ciliopathy as defined by two or more family members with hyperechogenic kidneys or cystic kidneys, with or without extrarenal features

 

Genetic sequencing methods

  1. Next Generation Sequencing (NGS)
  2. Targeted Gene Sequencing

This aims to identify potentially disease-causing genetic mutations in patients with primary proteinuric glomerular diseases which are either familial; of congenital or infantile-onset; or resistant to all forms of immunosuppressive therapy.

We will first screen >100 genes known to cause glomerular diseases using targeted gene sequencing. If no definitely or probably pathogenic variants were found in known genes, then exome sequencing may be performed to identify novel genes.

 

  1. Genome-wide association studies (GWAS)

This aims to identify genetic risk alleles that may be important in disease susceptibility in primary sporadic FSGS in Asia.

Please refer to our protocol for more detailed aims and methods

Please click here for the protocol.