Mendelian and Non mendelian Diseases Flashcards
A patient presents with gradually worsening muscle loss and weakness, muscles that often contract and are unable to relax, cataracts, intellectual disability and heart conduction problems. What is the most likely diagnosis? What is the mode of inheritance? What is the causative gene? What is required for full penetrance?
Myotonic Dystrophy Type 1
Autosomal Dominant
Expanded CTG repeats in DMPK gene
For full penetrance there must be 50 or more CTG repeats
What are special features of Autosomal Dominant disorders with triplet repeat amplification disorders?
Anticipation
Increased number of affected in successive generations
Incomplete penetrance
Variable expressivity
What are the triple repeat disorders? What nucleotide sequence is repeated? What genes are affect? List the mode of inheritance for all and requirement for FULL penetrance.
Huntington Disease; Autosomal dominant; CAG repeat in HD gene; Full penetrance= Greater than 40 repeats
Fragile X; X-Linked Dominant (though it may appear recessive due to anticipation and possible reduced penetrance); CGG repeat in FMR1 gene; Full penetrance= Greater than 200 repeats
Myotonic dystrophy; Autosomal dominant; CTG repeat in DMPK; Full penetrance= Greater than 50 repeats
Friedreich ataxia; Autosomal recessive; GAA repeat in FRDA; Full penetrance= Greater than 100 repeats
A patient presents with progressive motor disability with uncontrolled movement, mental disturbances, and changes in personality. What is the most likely diagnosis? What is the mode of inheritance? What is the causative gene? What is required for full penetrance? Which population is the disorder most common in?
Huntington’s Disease
Autosomal Dominant
CAG repeat in HD gene
Full penetrance= Greater than 40 repeats
Most common in people of European ancestry
What are the three main types of mosaicism?
Somatic, gonosomal, and germline
Is isodisomy clinically relevent in autosomal recessive or autosomal dominant?
Autosomal recessive
A patient presents with macroglossia, large abdominal organs, hemihyperplasia, and omphalocele. What is the most likely diagnosis? What is the mode of inheritance? What is the causative gene?
Beckwith-Weidemann syndrome
Paternal UPD chromosome 11p15 due to abnormal methylation maternal CDKN1C, H19, IGF2, AND KCNQ1OT1
What decreases mitochondrial heteroplasmy advantage?
Loss of mitochondrial over time
Why are phenotype-genotype correlations paticularly hard to establish with mitochondrial diseases?
Becuase many mitochondrial functions are encoded by nuclear genes, autosomal genes act as modifier of mitochondrial phenotype
List of mitochondiral diseases
- Leber’s hereditary optic atrophy
- Mitochondrial encephalopathy, lactic acidosis, and
stroke like syndrome (MELAS)
•Maternal Inherited Diabetes and Deafness (MIDD)
A patient presents with early-onset type 2 diabetes, impaired insulin secretion. The patient’s disorder displays incomplete penetrance due to heteroplasmy. What is the most likely diagnosis? What is the mode of inheritance? What is the causative gene?
Maternally Inherited Diabetes and Deafness (MIDD)
Mitochondrial
Different mitochondrial mutations
What are the three types of phenotypes associated with polygenic inheritance?
Polymorphic- combinations of polygenic alleles
Continuous (quantitative)- traits that exhibit a range of values
Discrete (qualitative)- traits that are converted to a dichotomous or bimodal phenotypic distribution a.k.a distinct features encoded by a single loci
What determines the risk of polygenic inheritance?
Parents who have several affected children will have more high risk alleles than parents with only on affected child
How do the phenomenons of dominancy and recessivity apply to polyenic inheritance?
No one gene is dominant or recessive to another
