These original educational practice questions demonstrate the explanation format and genetics reasoning used in our resources. They are not official certification examination items. References accompany the explanations where relevant.
Question 1 — Imprinting Mechanism
A child with Prader-Willi syndrome has two copies of chromosome 15, both inherited from the mother. Which mechanism best describes this result?
Answer: B — Maternal uniparental disomy
Both copies come from the mother, so this is maternal uniparental disomy. The result lacks the usual paternal contribution to the relevant imprinted region. A reverses parent of origin. C and D describe copy loss, while the case explicitly identifies two maternal copies of the relevant region.
The parent of origin matters even when copy number is two. See the imprinting and UPD guide for more.
Question 2 — Metabolic Pattern
A child develops hypoglycemia with inappropriately low ketones during an illness with poor intake. The acylcarnitine profile shows a prominent C8 elevation. Which diagnosis best fits?
Answer: A — Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
Fasting intolerance, hypoketotic hypoglycemia, and prominent C8 elevation support MCAD deficiency, a fatty acid oxidation disorder. VLCAD (B) is the nearest pathway alternative, but its acylcarnitine pattern centers on longer-chain species rather than a C8-predominant pattern. GSD I can also cause fasting hypoglycemia with relatively low ketones, often accompanied by lactic acidosis. It does not explain the characteristic C8-predominant acylcarnitine pattern in this vignette. Maple syrup urine disease (D) affects branched-chain amino acid metabolism and does not fit this acylcarnitine pattern.
Interpret the pattern with the clinical setting and confirm the diagnosis. Source: MCAD deficiency GeneReviews.
Question 3 — Disease Mechanism
A newborn has rhizomelic short stature, macrocephaly with frontal bossing, and a trident hand. Which mechanism is associated with the typical FGFR3 variants causing this presentation?
Answer: C — Gain of function
Achondroplasia is associated with gain-of-function FGFR3 variants. A, B, and D describe reduced receptor activity or dosage rather than the relevant gain-of-function mechanism. Learn the direction of the signaling change alongside the gene name. Source: achondroplasia GeneReviews.
Question 4 — Test Interpretation
A child has a strong clinical suspicion for an imprinting disorder. Routine sequence analysis is negative, and the laboratory confirms that methylation was not assessed. Which conclusion is most appropriate?
Answer: C
A negative result must be interpreted within the assay's capabilities. Sequence analysis does not automatically assess methylation. A, B, and D overstate the meaning of the result. Ask which relevant variant classes and mechanisms the laboratory actually evaluated. See the genetic test selection guide for more on assay limitations.
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