A 10-year-old boy is brought to the emergency department for new swelling in his right leg. He has a history of lens dislocation and intellectual disability. Physical examination demonstrates moderate, pitting edema from his right calf to his right thigh and a normal left lower extremity. In addition, the patient has a caved-in appearing chest wall. He has no family members with similar conditions. Ultrasound reveals a deep venous thrombosis in his right femoral vein. Further genetic testing reveals a single missense mutation in the gene coding for cystathionine beta-synthase enzyme. Which of the following is the most likely explanation for this patient's genetic defect affecting multiple tissues?

Question

A 10-year-old boy is brought to the emergency department for new swelling in his right leg.  He has a history of lens dislocation and intellectual disability.  Physical examination demonstrates moderate, pitting edema from his right calf to his right thigh and a normal left lower extremity.  In addition, the patient has a caved-in appearing chest wall.  He has no family members with similar conditions.  Ultrasound reveals a deep venous thrombosis in his right femoral vein.  Further genetic testing reveals a single missense mutation in the gene coding for cystathionine beta-synthase enzyme.  Which of the following is the most likely explanation for this patient's genetic defect affecting multiple tissues?

Quizplus · Accepted Answer

This patient presenting with skeletal abnormalities, lens dislocation, intellectual deficits, vascular thromboses, and a genetic defect in the cystathionine beta-synthase enzyme likely has homocystinuria. The occurrence of multiple, seemingly unrelated phenotypic manifestations, often in different organ systems, as a result of a single genetic defect is termed pleiotropy. Most syndromic genetic illnesses including homocystinuria exhibit pleiotropy. (Choice A) Dominant negative mutations occur when an abnormal gene negatively affects the product of the wild-type gene in the same cell. For example, certain oncogene p53 mutations can lead to translation of a protein product that prevents wild-type p53 from binding to the promoter of its target genes. (Choice B) Genetic linkage describes the tendency of alleles located near one another on the same chromosome to be inherited jointly. (Choice C) Penetrance refers to the proportion of individuals with a given genotype that express the associated phenotype. In incomplete penetrance, less than 100% of individuals with a given genotype express its associated phenotype. (Choice D) Locus heterogeneity refers to the ability of one disease or trait to be caused by mutations in multiple different genes. An example is familial hypercholesteremia, which can be caused by different mutations affecting cholesterol metabolism genes (eg, LDL receptor, apo B-100). (Choice F) Polyploidy occurs when more than 2 complete sets of homologous chromosomes exist within an organism or cell. In a partial hydatidiform mole, for example, there are cells of nonstandard ploidy (typically 69,XXX; 69,XXY; or 69,XYY). The chromosomes in this case are derived from 1 haploid maternal set and 2 haploid paternal sets of chromosomes. (Choice G) The law of segregation (Mendel's first law) describes the phenomenon whereby gametogenesis within the parent organism results in the separation of paired alleles so that each offspring inherits only half of each parent's genetic composition. Educational objective: Pleiotropy describes instances where multiple phenotypic manifestations result from a single genetic mutation. Most syndromic genetic illnesses exhibit pleiotropy. __________ References: Pleiotropy in complex traits: challenges and strategies. (http://www.ncbi.nlm.nih.gov/pubmed/23752797)

A 10-Year-Old Boy Is Brought to the Emergency Department for New