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 40-year old man presents to his primary care physician's office with a sixmonth history of 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 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 CAG Educational Objective: Anticipation refers to the phenomenon in which the severity of an inherited disease worsens over succeeding generations. References: First Aid 2014 page 84]]
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::