University:
Western Sydney University
Course:
MEDI 2003 | Clinical Sciences 2
Academic year:

2024
Views:

97

Pages:

2
Author:

Mariam A. A.

Renal Genetics Subtitles: Explain the one-hit vs. two-hit hypothesis. Review the genetics of autosomal dominant polycystic kidney disease. Review the role of renal genetics predisposition in the development of common renal diseases. Refer to mechanisms, but some extra notes. When would you consider genetic disease? Pre-implantation genetic diagnosis (PGD) scope. Two-hit hypothesis of polycystic kidney disease. Nodes and Text: One-hit vs. Two-hit Hypothesis: Ptx born with a germ line mutation in all of their K cells. One copy of PDK1 or PDK2 will have inherited mutation/variant. Overtime in a single cell in the kidney, the 2nd mutation/variant is acquired. Clinical Features: A typical clinical feature: 1st affected in family (de novo diseases). Unusual clinical picture. Family Planning: Evidence that genotype can assist in predicting prognosis. Pre-Implantation Genetic Diagnosis (PGD): IVF selection for a known chromosomal disorder or single gene disorder. IVF techniques: 5-day embryo, remove 8-10 cells, test DNA or chromosomes. Genetic disorder excluded: embryo implanted. Genetic disorder detected: embryo discarded. Two-Hit Hypothesis: Ptx born with a germ line mutation in all of their K cells. One copy of PDK1 or PDK2 will have inherited mutation/variant. Overtime in a single cell in the kidney, the 2nd mutation/variant is acquired. Causes cell to grow very large. Risk Alleles Subtitles: When to consider genetic disease? Nodes and Text: African Americans have a 25-35x risk of developing ESRF. 50-71% of AA have ESRF while 0.03% of Europeans. Is much of risk is related to two common alleles in the APOL-1 gene. Risk of kidney disease of person has 2 common alleles (both affected). A risk factor of AA carry at least 1 risk allele. Those with 2 risk alleles have about 15% risk of developing kidney disease. These alleles are protective against a type of sleeping sickness bound in Africa continent. When to consider genetic disease? Ptx with Hx of renal disease. Young ptx. Anyone with unexplained CKD. Multi-system disease.