Exam 1 (2/6) Flashcards
Mendelian phenotype
Controlled by one gene (monogenic)
Mendelian disease
Caused by mutation of a single gene / locus; mutated gene is (mostly) necessary and sufficient for disease onset
Classifications of peripheral neuropathies
- Acquired neuropathies
- Neuropathies associated with other disorders
- Inherited neuropathies
Charcot-Marie-Tooth (CMT) disease
Hereditary disorder giving rise to distal limb
weakness, maximal in the lower
extremities
Locus heterogeneity
A single disorder, trait, or pattern of traits caused by mutations in genes at different chromosomal loci
Allelic heterogeneity
A single disorder, trait, or pattern of traits caused by different mutations within a gene
Clinical heterogeneity
The production of clinically different phenotypes, even among patients with the same mutation
CMT1
Primary demyelination; defect in myelinating Schwann cell
CMT2
Primary axon loss; no demyelination; defect in axon
Male pedigree symbol
Square
Female pedigree symbol
Circle
Sex removed or unknown pedigree symbol
Diamond
Unaffected pedigree symbol
Unshaded
Affected pedigree symbol
Shaded
Carrier pedigree symbol
Shaded circle in center
Five major mendelian inheritance patterns
- Autosomal dominant
- Autosomal recessive
- X-linked dominant
- X-linked recessive
- Y-linked
Autosomal dominant
One mutant copy necessary and sufficient for disease; affected individual has one
affected parent; 50% chance of transmission to next generation
Autosomal recessive
Two mutant copies necessary and
sufficient for disease; affected individuals born to unaffected parents (carriers); siblings of affected individuals have a 25% chance of being affected
X-linked dominant
One mutant X is N/S; more females than males affected but females have milder phenotype; child of affected female has 50% chance of being affected regardless of sex; all daughters of affected males will be affected; all sons of affected males will be unaffected
X-linked recessive
One mutant X is N/S in the absence of an unmutated WT X; mainly affects males (hemizygous); affected males born to unaffected parents; females affected if father affected/mother carrier or WT X is inactivated; no male-to-male transmission
Y-linked
Affects only males; affected males always have an affected father and affected offspring
Explanations for simplex pedigree (only one affected individual)
- AR or XLR
- De novo AD mutation
- AD with low penetrance
- Phenocopy (nongenetic)
Incomplete penetrance
A subset of individuals with the mutation(s) (required genotype) do not develop the disease
Age of onset
Some phenotypes present at different life stages and the age of onset can vary (e.g., adult onset neurodegenerative disease)
