Molecular Pathology Practice Questions

Q: Which gene would you test if the patient has a family history of breast and ovarian cancer?

BRCA1/2. ***BRCA1/2*** - Mutations in **BRCA1** and **BRCA2** genes are responsible for the majority of hereditary breast and ovarian cancer syndromes (*Hereditary Breast and Ovarian Cancer syndrome*). [1] - Testing these genes is the standard procedure when a patient presents with a strong family history of both breast and ovarian cancers, as they are **tumor suppressor genes** involved in DNA repair. [1] ***P53*** - Mutations in the **TP53** gene are associated with **Li-Fraumeni syndrome**, which increases the risk for a wide spectrum of cancers, including breast cancer, sarcomas, brain tumors, and adrenocortical carcinoma. - While breast cancer is a component, Li-Fraumeni is less specifically linked to the combined presentation of breast and ovarian cancer compared to BRCA mutations. ***PTEN*** - Mutations in the **PTEN** gene cause **Cowden syndrome**, characterized by multiple hamartomas and an increased risk of breast, thyroid, and endometrial cancers. - Ovarian cancer is a less prominent feature of Cowden syndrome, making it a secondary consideration after BRCA testing. ***CDH1*** - Mutations in the **CDH1** gene (which encodes **E-cadherin**) are primarily associated with **Hereditary Diffuse Gastric Cancer (HDGC)**. - These mutations also confer an increased risk for **lobular breast cancer**, but they are not the primary drivers for a syndrome involving both significant breast and ovarian cancer risk.

Q: A 15-year-old tall boy with long limbs presents to the OPD. On ocular examination, bilateral ectopia lentis is noted. Which gene is most likely affected in this inherited disorder?

FBN1 (Fibrillin-1). ***FBN1 (Fibrillin-1)*** - The clinical triad of tall stature/long limbs (**Marfanoid habitus**) and **ectopia lentis** (lens dislocation) is characteristic of **Marfan syndrome** [1]. - Marfan syndrome is caused by an autosomal dominant mutation in the **FBN1 gene** on chromosome 15, which codes for the connective tissue protein **Fibrillin-1** [1]. *COL5A* - Mutations in **COL5A** (Type V collagen) are typically associated with the Classical type of **Ehlers-Danlos syndrome (EDS)**. - Clinical features of EDS primarily include **skin hyperextensibility** and **joint hypermobility**, which are not the most prominent features in this presentation. *PAX6* - The **PAX6 gene** is a master gene for eye development, and its mutation primarily causes **Aniridia** (absence of the iris) or other widespread ocular developmental defects. - Although ophthalmological findings are present, aniridia is not the key ocular finding, making PAX6 mutation an incorrect association. *TGF-β R2* - Mutations in **TGF-β R2** are linked to **Loeys-Dietz syndrome**, which involves severe **aortic root dilation** and craniocervical instability [1]. - While Loeys-Dietz syndrome presents with Marfanoid skeletal features, **ectopia lentis** is rare or absent, differentiating it from Marfan syndrome (FBN1) [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 153-154.

Q: The pedigree chart shown in the image demonstrates a specific pattern of inheritance. Which of the following conditions is most likely to follow this pattern of inheritance?

Kearns-Sayre syndrome. ***Kearns-Sayre syndrome*** - This condition is caused by large-scale deletions in **mitochondrial DNA (mtDNA)**, leading to a pattern of **maternal inheritance** (non-Mendelian) [1]. - Mitochondrial disorders are passed exclusively from the mother, affecting all offspring, which defines this specific inheritance pattern [1]. *Duchenne muscular dystrophy* - This follows an **X-linked recessive** pattern of inheritance, where the defective gene is located on the X chromosome [2]. - It primarily affects males, with mothers typically being asymptomatic carriers, clearly distinguishing it from mitochondrial inheritance [2]. *Huntington's disease* - This is an **autosomal dominant** disorder, meaning it is caused by a mutation on a non-sex chromosome and can be passed from either parent [3]. - It affects both males and females equally, with a 50% chance of transmission regardless of the child's sex [3]. *Marfan syndrome* - This is an **autosomal dominant** condition resulting from a mutation in the **FBN1 gene** (nuclear DNA) [3]. - The inheritance does not rely exclusively on the maternal line, as expected in an autosomal dominant Mendelian disorder [3]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 181. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 151. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 149-150.

Q: A 22-year-old tall male presents with long limbs, increased arm span, hypermobile joints, and high-arched palate. On examination, he has lens subluxation and a diastolic murmur suggestive of aortic root dilation. Which of the following genes is most likely mutated in this condition?

Fibrillin-1 (FBN1). ***Fibrillin-1 (FBN1)*** - The clinical presentation (tall stature, long limbs, increased arm span, aortic root dilation, and lens subluxation/ectopia lentis) is characteristic of **Marfan Syndrome** [1]. - Marfan syndrome is caused by an autosomal dominant mutation in the **FBN1 gene** on chromosome 15, which codes for the microfibrillar protein **fibrillin-1** [1]. *COL4A5* - Mutations in **COL4A5** (Type IV collagen) are associated with **Alport Syndrome**. - Alport syndrome primarily presents with **progressive sensorineural hearing loss**, ocular abnormalities (not typically lens subluxation), and **nephropathy** (hematuria/proteinuria). *COL1A1* - Mutations in **COL1A1** (Type I collagen) are most commonly associated with **Osteogenesis Imperfecta (OI)**. - OI is characterized by **recurrent fractures**, often with blue sclerae, hearing loss, and joint laxity, but not the specific cardiovascular and ocular features seen here. *Elastin* - Mutations in the **Elastin gene (ELN)** are responsible for **Supravalvular Aortic Stenosis (SVAS)**, often seen in **Williams Syndrome**. - Williams syndrome also involves intellectual disability and a characteristic 'elfin' facies, which are not mentioned in this patient's presentation. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 153-154.

Q: Which of the following is an incorrect gene-disease association?

TP53 - Mucosal Neuroma. ***TP53 - Mucosal Neuroma*** - This is an **incorrect association**. Mucosal neuromas are a hallmark feature of **Multiple Endocrine Neoplasia type 2B (MEN 2B)** [2]. - MEN 2B is caused by a germline gain-of-function mutation in the **RET proto-oncogene**, not the TP53 tumor suppressor gene (which is associated with **Li-Fraumeni syndrome**). *STK11 - Breast Cancer* - This is a **correct association**. Mutations in the **STK11** gene cause **Peutz-Jeghers syndrome (PJS)**. - Patients with PJS have a significantly increased risk of developing several malignancies, including gastrointestinal cancers and non-GI cancers like **breast cancer**. *PTEN - Thyroid Carcinoma* - This is a **correct association**. Germline mutations in the **PTEN** gene are responsible for **Cowden Syndrome**. - Cowden Syndrome is characterized by hamartomas and a high lifetime risk of developing cancers, most notably **follicular thyroid carcinoma** and breast cancer. *BRCA2 - Prostate Carcinoma* - This is a **correct association**. Germline mutations in **BRCA2** are strongly linked to hereditary breast and ovarian cancer syndromes [1]. - Men with **BRCA2** mutations have a substantially elevated risk of developing **prostate carcinoma**, often presenting with high-grade, aggressive disease. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Pancreas, pp. 898-899. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1139-1140.

Q: The karyotypic anomaly in the given image denotes which of the following diseases?

Cri du Chat Syndrome. ***Cri du Chat Syndrome*** - Caused by **deletion of the short arm of chromosome 5** (5p deletion), resulting in karyotype **46,XX/XY,del(5p)**. - Characteristic features include **cat-like cry** in infants, **microcephaly**, and severe **intellectual disability**. *Down Syndrome* - Results from **trisomy 21** with karyotype **47,XX/XY,+21**, not a deletion syndrome. - Clinical features include **flat facial profile**, **epicanthal folds**, and **cardiac defects**. *Edwards Syndrome* - Caused by **trisomy 18** with karyotype **47,XX/XY,+18**, involving chromosome 18 not chromosome 5. - Associated with **clenched fists**, **rocker-bottom feet**, and severe **growth retardation**. *Wolf-Hirschhorn Syndrome* - Results from **deletion of chromosome 4p** (4p deletion), not chromosome 5p deletion. - Characteristic **"Greek warrior helmet" facial appearance** and severe **developmental delays**.

Q: Which of the following conditions CAN BE transmitted as a recessive, sex-linked trait? I. Retinitis pigmentosa II. Colour blindness III. Cystic fibrosis IV. Duchenne muscular dystrophy Select the correct answer using the code given below :

I, II and IV. ***I, II and IV*** - All three conditions listed—**Retinitis Pigmentosa**, **Colour Blindness**, and **Duchenne Muscular Dystrophy**—can be inherited as recessive, **sex-linked traits**. - **Sex-linked inheritance** primarily refers to genes located on the **X chromosome**; males are more frequently affected because they have only one X chromosome. *II, III and IV* - This option incorrectly includes **Cystic Fibrosis**, which is an **autosomal recessive disorder**, not a sex-linked trait. - While **Colour Blindness** and **Duchenne Muscular Dystrophy** are sex-linked, their grouping with an autosomal condition makes this option incorrect. *I, II and III* - This option also incorrectly includes **Cystic Fibrosis** as a sex-linked trait. - **Retinitis Pigmentosa** and **Colour Blindness** can be sex-linked, but the inclusion of **Cystic Fibrosis** renders the entire option incorrect. *I, III and IV* - This option incorrectly includes **Cystic Fibrosis**; it is an **autosomal recessive condition**, not sex-linked. - Although **Retinitis Pigmentosa** and **Duchenne Muscular Dystrophy** are correctly identified as conditions that can be sex-linked, the incorrect inclusion of **Cystic Fibrosis** makes this option wrong.

Q: Which of the following syndromes are caused due to genomic imprinting? I. Rubinstein Taybi syndrome II. Prader-Willi syndrome III. Angelman syndrome IV. Edward syndrome Select the correct answer using the code given below :

II and III. ***II and III (Correct Answer)*** - **Prader-Willi syndrome** and **Angelman syndrome** are classic examples of disorders caused by **genomic imprinting** defects on chromosome 15 [1]. - **Prader-Willi syndrome** results from the loss of paternal 15q11-q13 expression, while **Angelman syndrome** results from the loss of maternal 15q11-q13 expression [1]. - Both conditions demonstrate parent-of-origin effects, where the same chromosomal region causes different phenotypes depending on whether the mutation is inherited from the mother or father [1]. *II and IV (Incorrect)* - While Prader-Willi syndrome is linked to genomic imprinting, **Edward syndrome** (Trisomy 18) is caused by a chromosomal abnormality (an extra copy of chromosome 18), not genomic imprinting. - Edward syndrome presents with distinct clinical features like **micrognathia** and **rocker-bottom feet**, different from imprinting disorders. *I and IV (Incorrect)* - **Rubinstein-Taybi syndrome** is caused by mutations in the **CREBBP** gene or deletion of 16p13.3, which are not related to genomic imprinting. - **Edward syndrome** is a chromosomal aneuploidy (Trisomy 18), not a disorder of genomic imprinting. *I and III (Incorrect)* - **Rubinstein-Taybi syndrome** is a genetic disorder caused by mutations in the CREBBP or EP300 genes, and it is not associated with genomic imprinting. - Only **Angelman syndrome** among these two options is caused by genomic imprinting. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 181-182.

Question 1

Which gene would you test if the patient has a family history of breast and ovarian cancer?

Accepted Answer

BRCA1/2

Answer

P53

Answer

CDH1

Answer

PTEN

Question 2

Which of the following is not an aneuploidy?

Accepted Answer

Bloom Syndrome

Answer

Trisomy 13

Answer

Trisomy 21

Answer

Klinefelter Syndrome

Question 3

A 15-year-old tall boy with long limbs presents to the OPD. On ocular examination, bilateral ectopia lentis is noted. Which gene is most likely affected in this inherited disorder?

Accepted Answer

FBN1 (Fibrillin-1)

Answer

COL5A

Answer

PAX6

Answer

TGF-β R2

Question 4

The pedigree chart shown in the image demonstrates a specific pattern of inheritance. Which of the following conditions is most likely to follow this pattern of inheritance?

Accepted Answer

Kearns-Sayre syndrome

Answer

Marfan syndrome

Answer

Duchenne muscular dystrophy

Answer

Huntington's disease

Question 5

A 22-year-old tall male presents with long limbs, increased arm span, hypermobile joints, and high-arched palate. On examination, he has lens subluxation and a diastolic murmur suggestive of aortic root dilation. Which of the following genes is most likely mutated in this condition?

Accepted Answer

Fibrillin-1 (FBN1)

Answer

COL4A5

Answer

Elastin

Answer

COL1A1

Question 6

Which of the following is an incorrect gene-disease association?

Accepted Answer

TP53 - Mucosal Neuroma

Answer

BRCA2 - Prostate Carcinoma

Answer

STK11 - Breast Cancer

Answer

PTEN - Thyroid Carcinoma

Question 7

The karyotypic anomaly in the given image denotes which of the following diseases?

Accepted Answer

Cri du Chat Syndrome

Answer

Down Syndrome

Answer

Edwards Syndrome

Answer

Wolf-Hirschhorn Syndrome

Question 8

A karyotype is shown in the image. What is the most likely diagnosis?

Accepted Answer

Klinefelter syndrome

Answer

Turner syndrome

Answer

Down syndrome

Answer

Cri-du-chat syndrome

Question 9

Which of the following conditions CAN BE transmitted as a recessive, sex-linked trait?
I. Retinitis pigmentosa
II. Colour blindness
III. Cystic fibrosis
IV. Duchenne muscular dystrophy

Select the correct answer using the code given below :

Accepted Answer

I, II and IV

Answer

II, III and IV

Answer

I, II and III

Answer

I, III and IV

Question 10

Which of the following syndromes are caused due to genomic imprinting?
I. Rubinstein Taybi syndrome
II. Prader-Willi syndrome
III. Angelman syndrome
IV. Edward syndrome

Select the correct answer using the code given below :

Accepted Answer

II and III

Answer

II and IV

Answer

I and IV

Answer

I and III

Molecular Pathology — MCQs

Molecular Pathology — MCQs

On this page

Practice by Chapter

Want unlimited practice?