WBR0087
| Author | [[PageAuthor::Ogheneochuko Ajari, MB.BS, MS [1] (Reviewed by Will Gibson, user: Jad Al Danaf)]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Biochemistry, MainCategory::Genetics |
| Sub Category | SubCategory::Neurology |
| Prompt | [[Prompt::A 40-year-old man presents to his primary care physician's office with a six month history of progressive difficulty with swallowing, involuntary jerky movements of the hands, and progressive memory loss. His father died of similar symptoms at the age of 55. This condition is an example of which of the following?]] |
| Answer A | AnswerA::Loss of heterozygosity |
| Answer A Explanation | [[AnswerAExp::Loss of heterozygosity refers to the loss of genetic material constituting a second, usually wild-type allele. One classic example of loss of heterozygosity occurs in the development of retinoblastoma. For most tumor suppressor genes, the complementary allele must be deleted/mutated before cancer develops.]] |
| Answer B | AnswerB::Locus heterogeneity |
| Answer B Explanation | [[AnswerBExp::Locus heterogeneity refers to the phenomenon in which mutations at different loci produce the same phenotype. Locus heterogeneity is exhibited by Marfan’s syndrome, MEN 2B and homocystinuria.]] |
| Answer C | AnswerC::Genomic imprinting |
| Answer C Explanation | [[AnswerCExp::Genomic imprinting is an epigenetic phenomenon by which certain genes can be expressed in a parent-of-origin-specific manner. The expression of one parental allele is often silenced by DNA methylation. Genomic imprinting is seen in Prader-Willi syndrome and Angelman syndrome where the differences in phenotype depend on whether the chromosome carrying a deletion is inherited from the mother or the father.]] |
| Answer D | AnswerD::Anticipation |
| Answer D Explanation | [[AnswerDExp::Anticipation refers to the phenomenon in which disease severity worsens or the age of onset of symptoms becomes earlier in succeeding generations. The patient in this vignette is exhibiting symptoms of Huntington's disease, a classic syndrome for genetic anticipation.]] |
| Answer E | AnswerE::Pleitropy |
| Answer E Explanation | [[AnswerEExp::Pleiotropy occurs when one gene influences multiple, seemingly unrelated phenotypic traits. Pleitropy is seen in phenylketonuria where a defect in a single gene causes severe cognitive abnormalities as well as separate dermatologic abnormalities.]] |
| Right Answer | RightAnswer::D |
| Explanation | [[Explanation::The patient in this vignette has Huntington’s disease, a uniformly fatal neurodegenerative trinucleotide repeat genetic disorder that affects muscle coordination and leads to cognitive decline. Symptoms manifest in affected individuals between the ages of 20 and 50. Clinical findings include depression, progressive dementia, choreiform movements, caudate atrophy and decreased levels of both GABA and Acetylcholine in the brain. It is a trinucleotide repeat disorder caused by (CAG)n repeats in the Huntingtin gene located on chromosome 4.
Expansion of this CAG triplet repeat stretch within the Huntingtin gene results in a different (mutant) form of the protein that gradually damages cells in the brain through mechanisms that are not fully understood. The disease is inherited in an autosomal dominant manner and displays genetic anticipation. Anticipation refers to the phenomenon in which an inherited disease strikes individuals earlier and with greater severity in succeeding generations. This anticipation is thought to be caused by polymerase "slippage" during DNA replication in germ cells, thereby increasing the length of the repeat segment. Wiki-mnemomic: You hunt animals and put them in the CAGe: Huntington Disease is a CAG repeat disorder. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Huntington's disease, WBRKeyword::Huntington disease, WBRKeyword::Genetics, WBRKeyword::Inherited, WBRKeyword::Anticipation, WBRKeyword::trinucleotide repeat disorders, WBRKeyword::Inheritance, WBRKeyword::Neurodegenerative |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |