WBR0087
| Author | [[PageAuthor::Ogheneochuko Ajari, MB.BS, MS [1] (Reviewed by Will Gibson, Jad Al Danaf, Rim Halaby, M.D. [2], and Yazan Daaboul)]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Biochemistry, MainCategory::Genetics |
| Sub Category | SubCategory::Neurology |
| Prompt | [[Prompt::A 40-year-old man is brought to his physician's office by his wife for aggressive behavior, involuntary rhythmic jerking movements of the hands, and memory loss that are progressively worsening for the past 6 months. The patient's father died of similar symptoms at the age of 55. This condition is an example of which of the following genetic disorders?]] |
| 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 observed in phenylketonuria where a defect in a single gene causes severe cognitive abnormalities as well as separate dermatological abnormalities.]] |
| Right Answer | RightAnswer::D |
| Explanation | [[Explanation::Huntington’s disease is an autosomal dominant neurodegenerative genetic disease caused by polyglutamine expansion in the gene for the huntingtin (HTT) protein. It is characterized by the presence of trinucleotide repeats (CAG) in the Huntingtin gene located on chromosome 4. Symptoms manifest in affected individuals between the ages of 20 and 50. Clinically, Huntington's disease is characterized by the presence of a triad: psychiatric symptoms, motor dysfunction, and cognitive impairment due to caudate atrophy and decreased levels of both GABA and acetylcholine 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::trinucleotide repeat disorders, WBRKeyword::Inheritance, WBRKeyword::Neurodegenerative |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |