1. c. Patients with the Ser810Lys mutation have severe hypertension, which present mostly before age 20. The mutation is not associated with neoplastic formation. The dominant forms of pseudohypoaldosteronism are secondary to the following inactivating mutations: ΔG1226, ΔT1597, C/T1831stop, and ΔA intron splice site. The mutation results in a constitutively activated mineralocorticoid receptor; however, it retains its normal activation by aldosterone.

2. a. All polymorphisms with a “star” *1 are considered to be wild-type by convention. Hence, all other variants are altered, leading to either excess, depressed, or absent production.

3. e. Individuals with CYP2C9*2 and CYP2C9*3 have an impaired metabolism of S-warfarin, which leads to an increased plasma concentration of the drug despite standard dosing. Hence, such patients will experience an increased risk for serious or life-threatening bleeding complications despite obtaining a standard dose of medication. The VKORC1 polymorphism likewise has a role in warfarin therapy.

4. c. Genetic equilibrium is a basic principle of population genetics. Violations of the Hardy-Weinberg law can cause deviations from expectation. Among such deviations are inbreeding/co-sanguinuity (increases homozygosity for all genes), small population size (can cause random change in genotypic frequency – also known as genetic drift), and assortative mating (causes an increase of homozygosity only of those genes involved in the trait). The law further assumes that there is no appreciable rate of mutation; changes in this manner would affect the allelic frequencies, which are assumed to be constant.

5. e. Paracentric inversion consists of an inversion within a given arm of the chromosome. Insertions “insert” additional chromosome, whereas duplication inserts a portion of duplicated chromosome. Isochromosomes lose one of the chromosome arms and contains a duplicate inverted other chromosome arm (e.g., 2p arms in mirror image at centromere).

6. d. The picture depicts a child with holoprosencephaly. Nonsyndromic forms of holoprosencephaly are predominantly autosomal dominant, with an incidence of 1 in 10,000 to 1 in 12,000 births. Autosomal recessive and X-linked recessive forms do occur, however are rare. It affects twice as many girls as it does boys. The facial dysmorphisms occur as a spectrum, with mild alterations including lack of frontal incisor, lack of superior labial frenulum, hypotelorism or hypertelorism, bifid uvula all the way to marked CNS alterations, including alobar holoprosencephaly. Sonic Hedgehog (SHH) mutations are loss-of-function mutations and account for nearly 40% of familial nonsyndromic autosomal dominant holoprosencephaly. Other genes implicated in this disease include ZIC2, PTCH, and TGIF.

7. a. Loss of the paternal allele of the PWS/AS region on chromosome 15 accounts for the syndrome; maternal uniparental disomy (˜ 25%) and paternal deletion of 15q11-q13 (˜ 70% to 80%) account for the brunt of alterations. An additional however small component (< 5%) imprinting defects are noted; however, mutations, per se, do not occur in PWS. The prevalence of PWS is 1/10,000 to 1/15,000. Hypogonadism is present in both males and females, with most individuals unable to reproduce.

8. b. Rituximab is directed against CD20 B-cell surface antigen and is used for therapy in non-Hodgkin lymphoma. The CD52 lymphocyte surface antigen antibody used for treatment of CLL and T-cell lymphomas is alemtuzumab (Campath).

9. d. Myotonic dystrophy type I is the most common muscular dystrophy presenting in adults. It is characterized by myotonia, progressive weakness, and atrophy of skeletal muscles, as well as systemic manifestations including cardiac involvement. The cardiac involvement initially manifests as asymptomatic ECG abnormalities, prolonged PR and QRS duration leading to arrhythmia, progressive heart block, and trial/ventricular fibrillation. Sudden death may occur as a consequence of myocardial fibrosis and degeneration of the cardiac-conduction system. The CTG triplet repeat expansion is found in the 3′ untranslated region of the DMPK (dystrophia myotonica protein kinase) gene.

10. c. KSS by rule is heteroplasmic. KSS is exceedingly rarely inherited maternally and if present, it is due to mtDNA duplication. Spontaneous mtDNA rearrangements/deletions are noted in ˜80% of cases. The most common deletion (˜ 30%) is 4.9kb in size.

11. a. RON (macrophage-stimulating 1 receptor, MST1R) is a member of the receptor tyrosine kinase gene family that includes the MET oncogene.

12. b. LOH testing required that a sample have two DNA strands of varying length of the region being amplified in the non-tumor sample in order to be informative. In this way, PCR amplification reveals two bands, both of different sizes, in this case in Nx2 bp difference. LOH would be considered when two bands were to be present in the non-tumor sample and one band to be present in the tumor sample. Because the normal sample in this question reveals a single band, it might be assumed that both strands are of the same length therefore uninformative; however, the region being testing may be missing from one of the chromosome arms, therefore producing a single PCR product. Neither sequencing nor new primer sets for the region will resolve such questions; however, testing on the level where chromosome copy number is determined (e.g., comparative genomic hybridization, karyotyping, copy number variant testing) should resolve such cases more definitively.

13. c. KRAS, an oncogene, is typically activated by mutation – methylation does not play a role in activating oncogenes. Hypermethylation of MLH1 (colon, endometrial cancer), P16 (esophageal, lung cancer), RB, and BRAC1 (breast ovarian cancer) are tumor suppressor genes that may either be inactivated by mutation or hypermethylation. Either path to inactivation leads to detrimental outcomes in these genes.

14. b. Indeed, no molecular based HSV

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