None listed
Conditions
Brief summary
Recent advances in genetic sequencing technology have resulted in remarkable improvements in the speed, throughput and cost of sequencing all, or part, of an individual's genome. Our hypothesis is that emerging high throughput sequencing technologies will lead to the rapid identification of new disease genes in genetic renal disease. This project will attempt to elucidate the genetic basis for inheritable kidney disease using next generation sequencing (NGS). The NGS employed may be targeted to a panel of genes of interest, to the whole exome (i.e. canonical protein-coding genes), or the entire genome. The patient cohort will include those whose family history and/or phenotype strongly suggests a genetic aetiology and in whom routine genetic testing is: a) not clinically available b) not feasible given high genetic heterogeneity of the suspected disorder, or c) has failed to arrive at a diagnosis for the likely disorder. Patients will be seen and assessed by a nephrologist and/or clinical geneticist in a Renal Genetics Clinic. Patients meeting minimum requirements for participation will be offered enrolment to the study and informed consent will be obtained. Once consent has been given, a DNA sample will be obtained via a blood test or buccal swab. The DNA will be analysed using NGS technologies. Where possible, family members including parents, siblings and possibly offspring of the affected individual will be recruited and included in the NGS testing. Genomic testing on first-degree relatives is necessary in most cases for the accurate interpretation of genetic variants found in the affected patient. Disease-causing mutations will be specifically sought in genes thought to be related to the patient's condition. If found, these variants will be confirmed with specific testing in a clinical laboratory, if available. Validation studies may be performed in a research capacity on selected novel potentially disease-causing variants or where disease pathobiology is not known. This will include patient-derived induced pluripotent stem cell (iPSC) validation after further patient consent for skin biopsy, urine sample, blood sample or buccal swab. iPSC technology enables ex vivo “disease in a dish” cellular and functional research of human disease owing to the ability to redifferentiate iPSC to many different cell types and thus model and validate how a genetic variant may mediate disease. Mutations previously reported to be disease-causing may also be discovered in genes not related to the patient's condition. Participants will be informed of known or expected, disease-causing variants in primary genes of interest. If chosen at the time of consent, participants will be informed of mutations in genes predicted to be associated with unrelated disease, and for which intervention is available.
Interventions
This project will attempt to elucidate the genetic basis for inheritable kidney disease using next generation sequencing (NGS). The NGS employed may be targeted to a panel of genes of interest, to the whole exome (i.e. canonical protein-coding genes), or the entire genome. The patient cohort will include those whose family history and/or phenotype strongly suggests a genetic aetiology and in whom routine genetic testing is:
a) not clinically available
b) not feasible given high genetic het
This project will attempt to elucidate the genetic basis for inheritable kidney disease using next generation sequencing (NGS). The NGS employed may be targeted to a panel of genes of interest, to the whole exome (i.e. canonical protein-coding genes), or the entire genome. The patient cohort will include those whose family history and/or phenotype strongly suggests a genetic aetiology and in whom routine genetic testing is: a) not clinically available b) not feasible given high genetic heterogeneity of the suspected disorder, or c) has failed to arrive at a diagnosis for the likely disorder. Patients will be seen and assessed by a nephrologist and/or clinical geneticist in a Renal Genetics Clinic. Patients meeting minimum requirements for participation will be offered enrolment to the study and informed consent will be obtained. Once consent has been given, a DNA sample will be obtained via a blood test or buccal swab. The DNA will be analysed using NGS technologies. Where possible, family members including parents, siblings and possibly offspring of the affected individual will be recruited and included in the NGS testing. Genomic testing on first-degree relatives is necessary in most cases for the accurate interpretation of genetic variants found in the affected patient.
Sponsors
Genetic Health Queensland, RBWH
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Diagnosis
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Two groups of individuals will be recruited for this study: - Candidates for participation in the protocol will be affected individuals whose family history and/or phenotype strongly suggests a genetic aetiology and in whom routine genetic testing is: a) not clinically available b) not feasible given the suspected disorder has high genetic heterogeneity, or c) if specific testing for the likely disorder has already failed to arrive at a diagnosis. - First-degree relatives of participating patients (father, mother, siblings, or sons and daughters of the patients). Patients will be seen and assessed by a nephrologist and/or clinical geneticist in a Renal Genetics Clinic.
Exclusion criteria
- Declination to participate in the study - An insufficient number of direct relatives willing/able to participate in the study. In most cases inclusion in this study will require the participation of the patient and both parents. However, in some cases a combination of factors including the structure of the family pedigree, the suspected mode of inheritance, and information available regarding the specific disease may provide the required level of genetic information and therefore warrant inclusion in the study. This will be determined on a case-by-case basis by the Principal Investigators.
Outcome results
None listed