A 21-year-old man has painless, rapid loss of central vision, first in the right eye and then, 6 weeks later, in the left. His 25-year-old sister lost vision the same way last year, and his maternal uncle went blind in his twenties; that uncle's daughter has two adult sons with normal vision. His parents see normally. Which pattern of inheritance best explains this family?

Mitochondrial (maternal) inheritance

Autosomal recessive inheritance

A newborn of a 41-year-old mother in a district hospital labour room has upslanting palpebral fissures, a flat facial profile, a single transverse palmar crease and hypotonia. Karyotype shows 47,XY,+21. What is the most common mechanism of this karyotype?

Maternal meiotic nondisjunction

Robertsonian translocation in a parent

Mitotic nondisjunction after fertilisation

Genetic disorders and immunopathology

19 NEET-PG practice questions on Genetic disorders and immunopathology, part of Pathology. The first 19 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Medium
A 19-year-old tall, thin college basketball player has an arm span greater than his height, long fingers, a pectus excavatum and upward displacement of both lenses. Echocardiography shows dilatation of the aortic root. A defect in which protein causes his condition?
1. AElastin
2. BType I collagen
3. CFibrillin-1
4. DType III collagen
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Answer: C · Fibrillin-1
Tall stature with long limbs and fingers, chest deformity, upward lens dislocation (ectopia lentis) and aortic root dilatation are features of Marfan syndrome, an autosomal dominant disorder caused by mutations of FBN1 on chromosome 15. Fibrillin-1 forms the scaffolding of microfibrils in elastic tissue and holds TGF-beta in an inactive form; defective fibrillin lets excess TGF-beta activity weaken the aortic media. The main cause of death is aortic dissection or rupture, so these patients need regular echocardiography, beta-blockers or losartan, and elective root repair when the aorta enlarges.
- A: Elastin mutations cause supravalvular aortic stenosis, as in Williams syndrome.
- B: Type I collagen defects cause osteogenesis imperfecta, with fractures and blue sclerae.
- D: Type III collagen defects cause vascular Ehlers-Danlos syndrome.
Question 2 · Medium
A 56-year-old man on maintenance haemodialysis for 12 years has pain and tingling in both hands at night, a positive Tinel sign at the wrists and bone cysts in the carpal bones on X-ray. Biopsy of the synovium shows Congo red-positive material. Which protein forms this amyloid?
1. ASerum amyloid A
2. BTransthyretin
3. CImmunoglobulin light chain
4. DBeta-2 microglobulin
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Answer: D · Beta-2 microglobulin
Beta-2 microglobulin, the light chain of HLA class I molecules, is normally cleared by the kidney, and conventional dialysis membranes remove it poorly. In long-term dialysis it accumulates and deposits as amyloid in joints, synovium, tendons and bone, giving carpal tunnel syndrome, arthropathy and bone cysts. High-flux membranes and kidney transplantation reduce the problem. The diagnosis matters because carpal tunnel release relieves the symptoms.
- A: Serum amyloid A forms AA amyloid in chronic inflammation, mainly affecting the kidney.
- B: Transthyretin forms hereditary and senile (wild-type) amyloid of nerves and heart.
- C: Light chains form AL amyloid in plasma cell disorders.
Question 3 · Hard
A 38-year-old man has burning pain and numbness in both feet for 2 years, now reaching his knees, with postural dizziness, alternating diarrhoea and constipation, and erectile dysfunction. His father had a similar illness in his forties and died of heart failure. There is no monoclonal protein on serum and urine immunofixation. Sural nerve biopsy shows Congo red-positive deposits. Which protein most likely forms these deposits?
1. ATransthyretin
2. BImmunoglobulin light chain
3. CSerum amyloid A
4. DBeta-2 microglobulin
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Answer: A · Transthyretin
A length-dependent painful sensory neuropathy with autonomic failure, an autosomal dominant family history with cardiac death and amyloid in the nerve, but no monoclonal protein, points to hereditary transthyretin (ATTR) amyloidosis. Mutant transthyretin, made mainly by the liver, misfolds and deposits in nerves and heart. Excluding AL amyloid by immunofixation is the key step because AL is treated quite differently. Options include transthyretin stabilisers such as tafamidis, gene-silencing drugs and, historically, liver transplantation; relatives should be offered genetic counselling.
- B: Light chain (AL) amyloid needs a plasma cell clone, and immunofixation shows no monoclonal protein.
- C: AA amyloid follows chronic inflammation and mainly affects the kidney.
- D: Beta-2 microglobulin amyloid occurs in long-term dialysis, with joint and carpal tunnel disease.
Question 4 · Medium
A 21-year-old man has painless, rapid loss of central vision, first in the right eye and then, 6 weeks later, in the left. His 25-year-old sister lost vision the same way last year, and his maternal uncle went blind in his twenties; that uncle's daughter has two adult sons with normal vision. His parents see normally. Which pattern of inheritance best explains this family?
1. AAutosomal dominant inheritance
2. BAutosomal recessive inheritance
3. CMitochondrial (maternal) inheritance
4. DX-linked recessive inheritance
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Answer: C · Mitochondrial (maternal) inheritance
Leber hereditary optic neuropathy causes subacute, painless, sequential central vision loss in young adults, mostly men. It is due to mutations in mitochondrial DNA genes for complex I of the respiratory chain, and mitochondria are passed on only through the ovum. So the disorder is transmitted through the female line to sons and daughters alike, while affected men never pass it on, which is why the uncle's grandsons are spared. Penetrance is higher in men, but women such as his sister can be affected. Because of heteroplasmy and other factors, many carriers, especially women, never lose vision.
- A: Autosomal dominant disease would pass from an affected man to about half his children.
- B: Autosomal recessive disease rarely appears across several generations along the maternal line.
- D: X-linked recessive disease would rarely affect a sister whose father is normal, and the uncle's grandsons would be at risk.
Question 5 · Easy
A newborn of a 41-year-old mother in a district hospital labour room has upslanting palpebral fissures, a flat facial profile, a single transverse palmar crease and hypotonia. Karyotype shows 47,XY,+21. What is the most common mechanism of this karyotype?
1. AMaternal meiotic nondisjunction
2. BRobertsonian translocation in a parent
3. CPaternal uniparental disomy
4. DMitotic nondisjunction after fertilisation
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Answer: A · Maternal meiotic nondisjunction
Free trisomy 21 (47 chromosomes) accounts for about 95% of Down syndrome, and nearly all of it comes from nondisjunction in meiosis, usually maternal meiosis I. The risk rises steeply with maternal age, as here. Translocation Down syndrome makes up about 4% and mosaicism, from mitotic nondisjunction, a small fraction. Free trisomy has a low recurrence risk, so parental karyotyping is not needed, unlike translocation cases.
- B: A Robertsonian translocation gives 46 chromosomes with the extra 21q attached to another chromosome.
- C: Uniparental disomy does not add a chromosome and is not how Down syndrome arises.
- D: Mitotic nondisjunction after fertilisation gives mosaicism, which is uncommon.
Question 6 · Medium
A 63-year-old woman has breathlessness, ankle oedema, an enlarged tongue with tooth indentations and bruising around both eyes. Urine protein is 5 g/day. Serum immunofixation shows a monoclonal lambda light chain, and the bone marrow has 12% plasma cells. Abdominal fat pad aspirate is Congo red-positive. What type of amyloid is this?
1. AAL amyloid
2. BATTR amyloid
3. CA-beta amyloid
4. DAA amyloid
Answer and explanation in LearnFree account
Question 7 · Medium
A 35-year-old farmer from Ratnagiri was given 10 vials of polyvalent anti-snake venom for a viper bite. He recovered and was discharged, but 9 days later returns with fever, an itchy rash, painful joints and enlarged lymph nodes. Urine shows 2+ protein and serum C3 is low. What is the mechanism of this illness?
1. ADeposition of antigen-antibody complexes
2. BIgE-mediated release of histamine
3. CAntibodies lysing his own red cells
4. DSensitised T cells attacking the skin
Answer and explanation in LearnFree account
Question 8 · Medium
A 27-year-old woman whose first child has Down syndrome attends a genetics clinic before planning another pregnancy. The child's karyotype is 46,XX,t(14;21), with the extra chromosome 21 material attached to chromosome 14. What is the most appropriate next step?
1. AKaryotype the child's siblings
2. BRepeat the child's karyotype
3. CReassure: recurrence risk is low
4. DKaryotype both parents
Answer and explanation in LearnFree account
Question 9 · Medium
A 34-year-old man has developed involuntary jerky movements and irritability. His father developed the same illness at 48 and died of it. Genetic testing shows a CAG repeat expansion in the HTT gene, longer than his father's. Which phenomenon explains his earlier onset?
1. AGermline mosaicism
2. BVariable penetrance
3. CAnticipation
4. DGenomic imprinting
Answer and explanation in LearnFree account
Question 10 · Easy
A 6-year-old girl whose grandfather has sputum-positive pulmonary tuberculosis is given an intradermal tuberculin (Mantoux) test in a paediatric OPD. When read at 72 hours there is 14 mm of induration at the site. Which type of hypersensitivity produces this reaction?
1. AType IV, T-cell mediated
2. BType III, immune complex
3. CType I, IgE mediated
4. DType II, antibody mediated
Answer and explanation in LearnFree account
Question 11 · Hard
In a community, an autosomal recessive disorder affects 1 in 2,500 births, and the population is in Hardy-Weinberg equilibrium. A man known by testing to be a carrier plans to marry an unrelated woman from the same community whose carrier status is unknown. What is the risk that their first child will be affected?
1. A1 in 25
2. B1 in 200
3. C1 in 100
4. D1 in 50
Answer and explanation in LearnFree account
Question 12 · Hard
A 17-year-old boy received an allogeneic bone marrow transplant from his HLA-matched sister for aplastic anaemia. On day 24 he has a maculopapular rash on his palms and soles, profuse watery diarrhoea and a bilirubin of 4.8 mg/dL. Consider four statements: 1. The donor's T cells are attacking the recipient's tissues. 2. Skin, liver and gut are the main target organs. 3. It is caused mainly by the recipient's antibodies against donor cells. 4. Irradiating cellular blood products for such patients prevents the transfusion-associated form of this disorder. Which statements are correct?
1. A1, 3 and 4 only
2. B1, 2 and 4 only
3. C1 and 4 only
4. D2 and 4 only
Answer and explanation in LearnFree account
Question 13 · Medium
A 28-year-old woman has weight loss, tremor, palpitations, a diffuse goitre with a bruit and bilateral proptosis. Serum TSH is suppressed and free T4 is high, and TSH receptor antibodies are strongly positive. Which type of hypersensitivity reaction underlies her disease?
1. AType II, antibody against a receptor
2. BType I, IgE on mast cells
3. CType III, immune complex deposition
4. DType IV, cytotoxic T-cell attack
Answer and explanation in LearnFree account
Question 14 · Medium
A 36-year-old man had a deceased-donor kidney transplant 7 weeks ago. His creatinine has risen from 1.2 to 2.4 mg/dL over a week. Biopsy shows a dense interstitial infiltrate of lymphocytes, with lymphocytes invading tubular epithelium, and C4d staining of peritubular capillaries is negative. Consider four statements: 1. Preformed antibodies are the main cause. 2. This is acute cellular rejection. 3. CD8+ cytotoxic T cells directly damage tubular cells. 4. Pulse intravenous methylprednisolone is the usual first treatment. Which statements are correct?
1. A3 and 4 only
2. B2, 3 and 4 only
3. C2 and 3 only
4. D1, 2 and 4 only
Answer and explanation in LearnFree account
Question 15 · Easy
A 52-year-old man with bronchiectasis following childhood tuberculosis has developed nephrotic syndrome. Renal biopsy shows amorphous, pale pink, acellular material in the glomeruli and vessel walls. Which stain and finding confirm the nature of this material?
1. APAS, magenta basement membranes
2. BCongo red, apple-green birefringence
3. CSilver stain, spiked membranes
4. DMasson trichrome, blue fibrosis
Answer and explanation in LearnFree account
Question 16 · Hard
A 25-year-old woman attends a genetics clinic during her first pregnancy. Her brother has haemophilia A, her father is unaffected and her mother has been confirmed as a carrier. The fetus is male on ultrasound, and she has not been tested herself. What is the probability that this boy will have haemophilia A?
1. A1 in 4
2. B1 in 8
3. C1 in 16
4. D1 in 2
Answer and explanation in LearnFree account
Question 17 · Medium
During a live-related kidney transplant at a tertiary hospital, the graft turns mottled and cyanotic within minutes of releasing the vascular clamps, and no urine is produced. An urgent biopsy shows neutrophils, fibrin and platelet thrombi in the glomerular capillaries. What is the most likely cause?
1. ACalcineurin inhibitor nephrotoxicity
2. BRecipient T cells primed over weeks
3. CPreformed antibodies against the graft
4. DDonor T cells attacking the recipient
Answer and explanation in LearnFree account
Question 18 · Easy
A 15-year-old boy with moderate intellectual disability and autistic features has a long face, prominent jaw, large protruding ears and enlarged testes. His mother's brother has a similar learning disability. Which genetic change most likely causes his condition?
1. ACGG repeat expansion in FMR1
2. BCAG repeat expansion in HTT
3. CExtra X chromosome (47,XXY)
4. DDeletion on chromosome 15q11-q13
Answer and explanation in LearnFree account
Question 19 · Medium
A 4-year-old boy was a floppy, poorly feeding baby. Now he eats constantly, is obese, short and has small hands and feet, with hypogonadism and mild learning difficulty. Methylation testing confirms the diagnosis, and a deletion of 15q11-q13 is found. On which parental chromosome is the deletion most likely?
1. APaternally derived chromosome 15
2. BMaternally derived chromosome 15
3. CEither chromosome, with equal effect
4. DBoth chromosomes 15
Answer and explanation in LearnFree account

Genetic disorders and immunopathology

A 19-year-old tall, thin college basketball player has an arm span greater than his height, long fingers, a pectus excavatum and upward displacement of both lenses. Echocardiography shows dilatation of the aortic root. A defect in which protein causes his condition?

A 56-year-old man on maintenance haemodialysis for 12 years has pain and tingling in both hands at night, a positive Tinel sign at the wrists and bone cysts in the carpal bones on X-ray. Biopsy of the synovium shows Congo red-positive material. Which protein forms this amyloid?

A newborn of a 41-year-old mother in a district hospital labour room has upslanting palpebral fissures, a flat facial profile, a single transverse palmar crease and hypotonia. Karyotype shows 47,XY,+21. What is the most common mechanism of this karyotype?

A 27-year-old woman whose first child has Down syndrome attends a genetics clinic before planning another pregnancy. The child's karyotype is 46,XX,t(14;21), with the extra chromosome 21 material attached to chromosome 14. What is the most appropriate next step?

A 34-year-old man has developed involuntary jerky movements and irritability. His father developed the same illness at 48 and died of it. Genetic testing shows a CAG repeat expansion in the HTT gene, longer than his father's. Which phenomenon explains his earlier onset?

A 6-year-old girl whose grandfather has sputum-positive pulmonary tuberculosis is given an intradermal tuberculin (Mantoux) test in a paediatric OPD. When read at 72 hours there is 14 mm of induration at the site. Which type of hypersensitivity produces this reaction?

A 28-year-old woman has weight loss, tremor, palpitations, a diffuse goitre with a bruit and bilateral proptosis. Serum TSH is suppressed and free T4 is high, and TSH receptor antibodies are strongly positive. Which type of hypersensitivity reaction underlies her disease?

A 52-year-old man with bronchiectasis following childhood tuberculosis has developed nephrotic syndrome. Renal biopsy shows amorphous, pale pink, acellular material in the glomeruli and vessel walls. Which stain and finding confirm the nature of this material?

A 15-year-old boy with moderate intellectual disability and autistic features has a long face, prominent jaw, large protruding ears and enlarged testes. His mother's brother has a similar learning disability. Which genetic change most likely causes his condition?