Biochem - Genetics (Autosomal-dominant diseases)

Question 1

What was the former name of Autosomal dominant polycystic kidney disease (ADPKD)?

Answer 1

Formerly known as adult polycystic kidney disease

Question 2

What is the main presentation of ADPKD, and what causes this?

Answer 2

Always bilateral, massive enlargement of kidneys due to multiple large cysts

Question 3

What mutations cause ADPK? On what chromosomes are they? What percentage of cases are attributed to each of these?

Answer 3

85% of cases are due to mutation in PKD1 (chromosome 16; Think: “16 letters in polycystic kidney”); Remainder due to mutation in PKD2 (chromosome 4)

Question 4

What defines familial adenomatous polyposis, and when does it occur?

Answer 4

Colon becomes covered with adenomatous polyps after puberty

Question 5

To what does familial adenomatous polyposis progress? How is this progression prevented?

Answer 5

Progresses to colon cancer unless colon is resected

Question 6

What mutation and chromosome are associated with familial adenomatous polyposis?

Answer 6

Mutations on chromosome 5 (APC gene); Think: “5 letters in ‘polyp’”

Question 7

What is the defect in familial hypercholesterolemia, and what effect does it have?

Answer 7

Elevated LDL due to defective or absent LDL receptor

Question 8

What are the 2 main clinical findings caused by familial hypercholesterolemia?

Answer 8

Leads to severe atherosclerotic disease early in life, and tendon xanthomas (classically in the Achilles tendon)

Question 9

What is Hereditary hemorrhagic telangiectasia? What is another name for it?

Answer 9

Inherited disorder of blood vessels; Also known as Osler-Weber-Rendu syndrome

Question 10

What are 6 clinical findings associated with hereditary hemorrhagic telangiectasia?

Answer 10

Findings: (1) telangiectasia (2) recurrent epistaxis (3) skin discolorations (4) atriovenous malformations (AVMs) (5) GI bleeding (6) hematuria

Question 11

What is the defect in hereditary spherocytosis, and what effect does it have?

Answer 11

Spheroid erythrocytes due to spectrin or ankyrin defect

Question 12

What are 2 clinical/lab findings associated with hereditary spherocytosis?

Answer 12

Hemolytic anemia; high MCHC

Question 13

What is the treatment for hereditary spherocytosis?

Answer 13

Treatment: splenectomy

Question 14

What are 5 clinical/lab findings associated with Huntington disease?

Answer 14

Findings: (1) depression, (2) progressive dementia, (3) choreiform movements, (4) caudate atrophy, and (5) low levels of GABA and ACh in the brain

Question 15

On what chromosome is the Huntington gene?

Answer 15

Gene on chromosome 4; Think: “Hunting 4 food”

Question 16

What kind of repeats are associated with Huntington disease? What effect do increasing number of repeats have?

Answer 16

Trinucleotide repeat disorder: (CAG)n. Increased repeats –> Decreased age of onset

Question 17

What is the defect in Marfan syndrome, and what effects does it have?

Answer 17

Fibrillin-1 gene mutation –> connective tissue disorder affecting skeleton, heart, and eyes

Question 18

What are 4 physical findings associated with Marfan syndrome?

Answer 18

Findings: (1) tall with long extremities (2) pectus excavatum (3) hypermobile joints (4) Long, tapering fingers and toes (arachnodactyly)

Question 19

What aortic finding is associated with Marfan syndrome, and what causes it?

Answer 19

Cystic medial necrosis of aorta –> aortic incompetence and dissecting aortic aneurysms

Question 20

What cardiac finding is associated with Marfan syndrome?

Answer 20

Floppy mitral valve

Question 21

What ocular finding is associated with Marfan syndrome?

Answer 21

Subluxation of lenses, typically upward and temporally

Question 22

What is MEN, and what are the types of MEN? In general, what characterizes them?

Answer 22

Multiple endocrine neoplasias (MEN); Several distinct syndromes (1, 2A, 2B) characterized by familial tumors of endocrine glands, including those of the pancreas, parathyroid, pituitary, thyroid, and adrenal medulla.

Question 23

Which what gene is MEN 2A associated? What other type of MEN is also associated with this gene?

Answer 23

MEN 2A and 2B are associated with ret gene

Question 24

What is another name for Neurofibromatosis type 1?

Answer 24

Neurofibromatosis type 1 (von Recklinghausen disease)

Question 25

What is Neurofibromatosis type 1, and what 2 main physical findings characterize it?

Answer 25

Neurocutaneous disorder characterized by cafe-au-lait spots and cutaneous neurofibromas

Question 26

What is the mode of inheritance, penetrance, and expression of neurofibromatosis type 1?

Answer 26

Autosomal dominant, 100% penetrance, variable expression

Question 27

What gene mutations cause Neurofibromatosis type 1, and on what chromosome is the gene found?

Answer 27

Caused by mutations in the NF1 gene on chromosome 17; Think: "17 letters in 'von Recklinghausen'"

Question 28

What are 4 clinical findings associated with Neurofibromatosis type 2?

Answer 28

Findings: (1) bilateral acoustic schwannomas (2) juvenile cataracts (3) meningiomas (4) ependymomas

Question 29

What gene mutations cause Neurofibromatosis type 2, and on what chromosome is the gene found?

Answer 29

NF2 gene on chromosome 22; Think: "type 2 = 22"

Question 30

What is Tuberous sclerosis, and what finding characterizes it?

Answer 30

Neurocutaneous disorder with multi-organ system involvement, characterized by numerous benign hamartomas

Question 31

What is the penetrance and expression of Tuberous sclerosis?

Answer 31

Incomplete penetrance, variable expression

Question 32

What characterizes von Hippel-Lindau disease?

Answer 32

Disorder characterized by development of numerous tumors, both benign and malignant

Question 33

With what mutation is von Hippel-Lindau disease associated, and on what chromosome is this gene found?

Answer 33

Associated with deletion of VHL gene (tumor suppressor) on chromosome 3 (3p); Think: "Von Hippel-Lindau = 3 words for chromosome 3"