Main Research Project:
GENETIC GLOMERULAR DISEASE
There is no age limit for recruited subjects. Adult subjects are welcome.
- Nephrotic syndrome onset <1y
- Initial-onset (no late-onset) steroid-resistant nephrotic syndrome
- Persistent subnephrotic proteinuria with ≥ one of the following:
- onset <3 years old
- significant family history (of neurosensory hearing loss, proteinuria, hematuria and/or CKD)
- Parental consanguinity
- significant extrarenal manifestations (relevant)
- 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.
Availability of histological evidence is highly recommended, but not mandatory. 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 below for more information on subject recruitment.
GENETIC CYSTIC RENAL DISEASE
We are exploring the possibility of including genetic cystic disease in our network. There is a possibility of offering genetic sequencing for such cases.
1. Individuals with Autosomal Recessive Polycystic Kidney Disease (ARPKD) as defined by
- typical findings on renal imaging AND
- 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.
2. Individuals with nephronophthisis related ciliopathy as defined by
- Hyperechogenic kidneys with normal or reduced size and corticomedullary cysts AND one or more of the following extrearenal features
- Liver fibrosis
- Retinitis pigmentosa or retinal dystrophy/degeneration
- Structural brain abnormalities
- Abnormalities of left-right patterning (also known as heterotaxy) eg dextrocardia, situs inversus
3. 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
Note: There is no upper limit to the current age of the patients
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.
3. 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.