WBR0087
| Author | [[PageAuthor::Ogheneochuko Ajari, MB.BS, MS [1]]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Biochemistry, MainCategory::Genetics |
| Sub Category | SubCategory::Neurology |
| Prompt | [[Prompt::A 56-year old man presents to the physicians office with a history of difficulty with swallowing, involuntary jerky movements of the hands, progressive loss of speech and memory. His father died of similar symptoms and his symptoms is said to be worse than his father’s. 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. It is an example of anticipation where the severity of the disease worsens or age of onset of disease is earlier in succeeding generations. Symptoms manifest in affected individuals between the ages of 20 and 50. It is a trinucleotide repeat disorder (CAG)n with the gene located on chromosome 4. Findings include depression, progressive dementia, choreiform movements, caudate atrophy and decreased levels of GABA and Ach in the brain. Educational Objective: Anticipation refers to the phenomenon in which the severity of an inherited disease worsens over succeeding generations. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Huntington's disease, WBRKeyword::Huntington disease, WBRKeyword::Genetics, WBRKeyword::Inherited, WBRKeyword::Anticipation, WBRKeyword::Inheritance, WBRKeyword::Neurodegenerative |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |