A 5-year-old boy presents with delayed walking and calf pseudohypertrophy. Family history is significant for an uncle who died young from muscle weakness.
What inheritance pattern does DMD follow?
What genetic test can detect large deletions/duplications in the DMD gene?
What lab test may be elevated in DMD?
A: X-linked recessive
A: MLPA (Multiplex Ligation-dependent Probe Amplification)
A: Creatine kinase (CK)
A newborn presents with ambiguous genitalia. Ultrasound shows no uterus. Parents are non-consanguineous and healthy.
What initial genetic test is most appropriate?
What additional targeted test could assess for specific deletions (e.g., SRY gene)?
A: Karyotype to determine chromosomal sex
A: FISH or gene-specific sequencing
A couple is planning to conceive. The woman is African American and has a family history of sickle cell disease. You order hemoglobin electrophoresis, and she is found to be a carrier.
What is the inheritance pattern of sickle cell disease?
What should be the next step in management?
If both are carriers, what reproductive options might you discuss?
A: Autosomal recessive
A: Test the partner for carrier status (hemoglobin electrophoresis)
A: Referral for genetic counseling, preimplantation genetic testing (PGT), or prenatal diagnostic testing (CVS/amniocentesis)
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A 42-year-old woman presents to discuss her family history of breast and ovarian cancer. Her mother was diagnosed at 45 and her sister at 38.
What type of inheritance pattern do BRCA1/2 mutations follow?
What genetic test would you recommend for this patient?
If she tests positive, what interventions might be considered?
A: Autosomal dominant
A: BRCA1/2 sequencing via next-generation sequencing (NGS)
A: Increased surveillance (e.g., breast MRI), risk-reducing surgery, chemoprevention, or referral to genetics.
A 2-year-old child is brought in for evaluation due to speech delay and dysmorphic facial features. Family history is negative for genetic conditions. The child had normal newborn screening.
What is the first-line genetic test to order for evaluating this child?
Why wouldn’t karyotyping be the best first test?
If microarray is normal, what gene-level test might be considered next?
A: Chromosomal microarray (CMA) – best for evaluating developmental delay, congenital anomalies.
A: It has lower resolution than microarray and may miss submicroscopic copy number changes.
A: Exome or gene panel sequencing, depending on suspected syndrome.
A 10-week pregnant patient presents to your clinic for her first prenatal visit. She is 35 years old and asks about screening options for genetic conditions like Down syndrome.
Which non-invasive screening test would you offer at this point in her pregnancy to assess for trisomy 21, 18, and 13?
Is this test diagnostic?
What diagnostic test could be offered between 10–13 weeks?
A: NIPT (Non-Invasive Prenatal Testing) – blood test, starting from 9–10 weeks.
A: No, NIPT is a screening test. Positive results must be confirmed with CVS or amniocentesis.
A: Chorionic Villus Sampling (CVS)
Q6: Why do mitochondrial disorders only get passed down from mothers?
A: Because mitochondria (and their DNA) are inherited maternally, through the egg.
Q5: What inheritance pattern is most likely if multiple generations are affected and both males and females are affected?
A: Autosomal dominant
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Q3: What are the advantages of using microarray over karyotyping?
A: Microarray has higher resolution and can detect smaller copy number changes that karyotyping might miss.
Q2: Why might a couple with a balanced translocation experience multiple miscarriages?
A: Even though there’s no net loss/gain of genetic material in a balanced translocation, gametes may receive unbalanced chromosomes, leading to nonviable embryos.
Q1: Why is NIPT considered a screening test and not diagnostic?
A: Because it cannot confirm a diagnosis; it only estimates risk. Positive results require confirmation via CVS or amniocentesis.
Q30: What is a nonsense mutation?
A30: Mutation introduces a premature stop codon.
Q29: What is a missense mutation?
A29: One amino acid is substituted for another.
The “sense” (meaning) of the codon changes → codes for a different amino acid
🧩 The protein may still be made but could function differently.
📌 Example:
Original codon: GAG = Glutamic acid
Mutated codon: GTG = Valine
⇒ Result: Missense (like in sickle cell disease)\
Missense is like using the wrong word in a sentence — it might still make sense, just differently.
“M” = Modified protein
Q28: What is a frameshift mutation?
A28: Insertion or deletion shifts the reading frame, usually leading to a premature stop codon.
The entire sentence loses meaning after the mutation. That’s a frameshift — everything downstream is affected.
Frameshift = Everything F’d”
Harsh but memorable: the frame is shifted, and the whole protein is usually functionally destroyed.
Affects everything after the mutation, not just one codon.
Q27: What is a balanced translocation?
A27: Chromosomal segments are exchanged with no net gain/loss of DNA.
Q26: What is aneuploidy?
A26: Abnormal number of chromosomes (e.g., Trisomy 21, Turner syndrome)
Q25: What does MLPA detect?
A25: Exon-level deletions or duplications in specific genes
Q24: What does sequencing detect?
A24: Point mutations and small variants in DNA
Q23: What does FISH test for?
A23: Specific small deletions or duplications (targeted test)
Q22: What is microarray testing best for?
A22: First-line test for copy number changes; detects unbalanced chromosomal changes
Q21: What does karyotyping detect?
A21: Large chromosomal abnormalities like aneuploidy, translocations
Q20: What are examples of multifactorial conditions?
A20: Cleft lip/palate, isolated congenital heart defect
