Genetics II

Question 1

What are the symptoms of Prader Willi Syndrome?

Answer 1

Mental retardation, hyperphagia, obesity, hypogonadism, hypotonia (due to paternal deletion) (p.83)

Question 2

What are the symptoms of Angelman’s Syndrome?

Answer 2

Mental retardation, seizures, ataxia, innapropriate laughter (due to maternal deletion) (p.83)

Question 3

What are the characteristics associated with an autosomal dominant mode of inheritance?

Answer 3

Often due to defect in structural genes. Many generations, both males and females are affected. Diseases are often pleotropic and a family history is crucial to diagnosis (p.84)

Question 4

What are the characteristics associated with an autosomal recessive mode of inheritance?

Answer 4

Often due to enzyme deficiencies. Usually only seen in one generation. Pathology is commonly more severe than Autosomal Dominant disorders (patients often present in childhood) (p.84)

Question 5

What are the characteristics associated with an X-linked recessive mode of inheritance?

Answer 5

Sons of heterozygous mothers have a 50% chance of being affected. No male-male transmission. Usually more severe in males and females must be homozygous to be affected (p.84)

Question 6

What are the characteristics associated with an X-linked dominant mode of inheritance?

Answer 6

Transmitted through both parents. Either male of female offspring of the affected mother may be affected. All female offspring of the affected father are affected (p.84)

Question 7

What are the characteristics associated with a mitochondrial mode of inheritance?

Answer 7

Transmitted only through the mother. All offspring of an affected mother show signs of disease. Often caused by failures in oxidative phosphorylation and expression can be variable in a population due to heteroplasmy (p.84)

Question 8

Name and describe an X-linked Dominant disorder.

Answer 8

Hypophosphatemic rickets- formerly known as Vitamin D-resistant rickets. Results in increased phosphate wasting at proximal tubule and causes a rickets-like presentation (p.84)

Question 9

Name a describe the most common class of mitochondrial disorders.

Answer 9

Mitochondrial myopathies. Rare disorders that are often present with myopathy and CNS disease. Muscle biopsy often shows “ragged red fibers” (p.84)

Question 10

What is the pathology associated with achondroplasia?

Answer 10

Cell signalling defect of fibroblast growth factor (FGF) receptor 3 (p.85)

Question 11

What is the clinical manifestation of achondroplasia?

Answer 11

Dwarfism- short limbs, larger head, normal trunk size (p.85)

Question 12

What is the most common factor associated with achondroplasia?

Answer 12

Advanced paternal age (p.85)

Question 13

Describe the pathology of autosomal dominant polycysitc kidney disease (ADPKD) and the classic symptoms.

Answer 13

Always bilateral, massive enlargement of kidneys due to multiple large cysts. Patient presents with flank pain, hematuria, hypertension, progressive renal failure (p.85)

Question 14

What is the most common genetic mutation associated with ADPKD?

Answer 14

85% of cases are due to a mutation in PKD1 (chromosome 16) (p.85)

Question 15

What are some clinical associations of ADPKD?

Answer 15

Polycystic liver disease, berry aneurysms, mitral valve prolapse (p.85)

Question 16

What is Familial adenomatous polyposis?

Answer 16

An autosomal dominant condition where the colon becomes covered with adenomatous polyps after puberty. It will progress to colon cancer unless colon is resected (p.85)

Question 17

What mutation is associated with familial adenomatous polyposis?

Answer 17

Mutation on chromosome 5 (APC gene) (p.85)

Question 18

What is familial hypercholesterolemia (hyperlipidemia type IIA)?

Answer 18

An autosomal dominant condition that causes elevated LDL due to defective or absent LDL receptor. Heterozygotes have cholesterol levels of about 300mg/dL; homozygotes (rare) have cholesterols of 700+ (p.85)

Question 19

What is the classic physical presentation of familial hypercholesterolemia (hyperlipidemia type IIA)?

Answer 19

Severe atherosclerotic disease early in life, tendon xanthomas (classically in the achilles tendon), and possibly MI before 20 years (p.85)

Question 20

Describe the condition of Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome).

Answer 20

An autosomal dominant condition characterized by the disorder of blood vessels. Findings include telangectasias, recurrent epistaxis, skin discolourations, AVMs (p.85)

Question 21

Describe the pathology of hereditary spherocytosis.

Answer 21

An autosomal dominant condition that results in spheroid erythrocytes due to a spectrin or ankyrin defect (p.85)

Question 22

What is the clinical presentation of hereditary spherocytosis?

Answer 22

Hemolytic anemia, increased MCHC (p.85)

Question 23

What is the treatment for hereditary spherocytosis?

Answer 23

Splenectomy is curative (p.85)

Question 24

Describe the pathology of Huntingtons disease.

Answer 24

Caudate atrophy, decreased levels of GABA and Ach in the brain (p.85)

Question 25

What is the genetic mutation associated with Huntingtons disease?

Answer 25

CAG trinucleotide repeat on chromosome 4 (p.85)