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::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. His symptoms have been progressively worsening for the past 6 months. The patient's father died of similar symptoms at the age of 55. The patient does not smoke cigarettes and only drinks alcohol occasionally. He denies use of medications or illicit drugs. The patient's 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 classical 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 father or the mother.]] |
| 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 (HD) is an autosomal dominant neurodegenerative genetic disease caused by polyglutamine expansion in the coding region of the gene IT15 that codes for the huntingtin (HTT) protein. Huntington's disease is characterized by the presence of unstable trinucleotide repeats (CAG) in the Huntingtin (HTT) gene located on the short arm of chromosome 4 (4p63). The CAG repeat length and paternal transmission are both significantly correlated with the onset of symptoms. HD is thus a classical example of anticipation, defined as the more severe and/or earlier onset of symptoms in successive generations within a pedigree.
Most patients with the HD mutation lead a normal life during early adulthood. Symptoms manifest in affected individuals between the ages of 20 and 50. Clinically, Huntington's disease is characterized by the presence of the triad: psychiatric symptoms, motor dysfunction, and cognitive impairment due to caudate atrophy and decreased levels of both GABA and acetylcholine in the brain. Ranen NG, Stine OC, Abbott MH, et al. Anticipation and instability of IT-15 (CAG)n repeats in parent-offspring pairs with Huntington disease. Am J Hum Genet.1995;57(3):593-602. First Aid 2014 page 84]] |
| 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:: |