Biochem - Genetics (Modes of inheritance)

Question 1

What often causes autosomal dominant disorders?

Answer 1

Often due to defects in structural genes

Question 2

What is the pattern of affected individuals given an autosomal dominant mode of inheritance?

Answer 2

Many generations, both male and female, affected.

Question 3

What characteristic/genetic term often describes the genes associated with autosomal dominant disorders?

Answer 3

Often pleiotropic

Question 4

What piece of clinical inquiry is crucial to diagnosis of autosomal dominant disorders?

Answer 4

Family history crucial to diagnosis

Question 5

What percentage of offspring from 2 carrier parents are affected by an autosomal recessive disorder?

Answer 5

25% of offspring from 2 carrier parents are affected.

Question 6

What often causes autosomal recessive disorders?

Answer 6

Often due to enzyme deficiencies

Question 7

What is the pattern of affected individuals given an autosomal recessive mode of inheritance?

Answer 7

Usually seen in only 1 generation

Question 8

How do autosomal recessive disorders compare to autosomal dominant disorders in terms of severity?

Answer 8

Commonly more severe than dominant disorders

Question 9

When do patients often present with autosomal recessive disorders?

Answer 9

Patients often present in childhood

Question 10

What increases risk of autosomal recessive disorders?

Answer 10

Increased risk in consanguineous families

Question 11

What percentage of sons of heterozygous mothers are affected with X-linked recessive disorder?

Answer 11

Sons of heterozygous mothers have a 50% chance of being affected

Question 12

What pedigree finding characterizes the pattern of affected individuals in X-linked recessive disorders?

Answer 12

No male-to-male transmission

Question 13

In what patient population are X-linked recessive disorders commonly more severe?

Answer 13

Commonly more severe in males

Question 14

What is usually required for females to be affected by X-linked recessive disorders?

Answer 14

Females usually must be homozygous to be affected

Question 15

Describe the transmission of X-linked dominant disorders, answering the following: Who transmits? To whom do they transmit?

Answer 15

Transmitted through both parents. Mothers transmit to 50% of daughters and sons; fathers transmit to all daughters but no sons

Question 16

What is the classic example of a X-linked dominant disorder? Give the current and former names of this disorder.

Answer 16

Hypophosphatemic rickets - formerly known as vitamin D-resistant rickets

Question 17

What defines hypophosphatemic rickets? In brief, how does it present?

Answer 17

Inherited disorder resulting in increased phosphate wasting at proximal tubule; Results in rickets-like presentation

Question 18

Describe the transmission of Mitochondrial inheritance disorders, answering the following: Who transmits? To whom do they transmit?

Answer 18

Transmitted only through the mother. All offspring of affected females may show signs of disease.

Question 19

What kind of expression occurs in mitochondrial inheritance disorders, and why?

Answer 19

Variable expression in a population or even within a family due to heteroplasmy

Question 20

What is a classic example of a mitochondrial inheritance disorder?

Answer 20

Mitochondrial myopathies

Question 21

What kind of inheritance mode do mitochondrial myopathies have? How common are they? How do they present?

Answer 21

Mitochondrial inheritance; Rare disorders; Often present with myopathy, lactic acidosis, and CNS disease

Question 22

What causes mitochondrial myopathies?

Answer 22

Secondary to failure in oxidative phosphorylation

Question 23

What histological finding characterizes mitochondrial myopathies?

Answer 23

Muscle biopsy often shows “ragged red fibers”