Atypical mendelian inheritance

Question 1

Define genetic anticipation

Answer 1

increasing severity and earlier age of onset of a disease in successive generations

Question 2

List examples of diseases with genetic anticipation

Answer 2

• Huntington disease
• Fragile X
• Myotonic dystrophy

Question 3

What are the common features of diseases with genetic anticipation?

Answer 3

All include neurological symptoms

the presence of tract of trinucleotide repeat units that lie within, or adjacent to a disease associated gene

Question 4

What is the common trigger for diseases with genetic anticipation?

Answer 4

Expansion of the trinucleotide tract beyond a certain size, resulting in it becoming a pathogenic mutation

Question 5

What is pseudodominant inheritance

Answer 5

Disease appears to be autosomal dominant, but actually autosomal recessive

Question 6

What is the common cause of pseudodominant inheritance

Answer 6

A high carrier frequency in the population, making it common for affected individuals to have affected children

Question 7

Name an example of a pseudodominant inherited disease

Answer 7

• Glibert syndrome (jaundice)

Question 8

Describe mitochondrial inheritance

Answer 8

only inherited from the mother but to variable extents

Question 9

Describe the mitochondrial genome

Answer 9

• much smaller genome
• circular
• 37 genes
• no introns

Question 10

What are the commonly affected regions with mitochondrial disorders?

Answer 10

• muscle
• brain
• eyes

Question 11

How do mitochondrial disease occur?

Answer 11

Defective funtion of the mitochondiral respiratory chain

Question 12

Name an example of a mitochondrial disorder

Answer 12

Leigh’s disease

• MT-ATP6 gene mutated in mitochondrial DNA
• product = ATP synthase

Question 13

Define mosaicism

Answer 13

genetic abnormality that arises during mitosis, post-fertilisation

N.b individuals possess both a normal cell line, and a genetically abnormal cell line

Question 14

What is the clinical consequence of mosaicism?

Answer 14

only some of the individuals cells may exhibit the phenotypic characteristics of a particular genetic condition

Question 15

How might offspring inherit the mosaicism mutation?

Answer 15

If the mosaicism is present in the gonads

N.B - the mutation would then be present in all of the child’s cells

Question 16

Define gonadal mosaicism

Answer 16

Phenotypically healthy individual may posses a genetic abnormality that is present in a proportion of their germ cells

Question 17

How does gonadal mosaicism affect offspring?

Answer 17

A disease may be present in more than one of the children of a clinically unaffected individual

Question 18

What are modifier genes?

Answer 18

genetic varients that can affect the manifestation of a disorder, such as

• age of onset
• range or severity of symptoms
• rate of disease progression

Question 19

What are susceptibility genes?

Answer 19

Those that alter the liability to develop the condition rather than altering the phenotype of the disease

Question 20

What processes may products of modifier genes alter?

Answer 20

• splicing
• transcription
• translation
• transport
• post-translational modification
• secretion
• activation
• degradation

Question 21

What is digenic inheritance?

Answer 21

Clinical condition that may arise from the interaction of different genes

Question 22

What is pseudoautosomal inheritance?

Answer 22

mutations of genes within the pseudoautosomal regions of the X and Y chromosome are inherited in an autosomal-like fashion

Question 23

What is the pseudoautosomal region of the X and Y chromosomes

Answer 23

The area in which recombination of the X and Y chromosomes can only take place

Question 24

How do mutations of genes within the pseudoautosomal regions of the X and Y chromosomes occur?

Answer 24

The 29 genes in this region escape X inactivation and are present on both the X and Y chromosomes

Question 25

Name some examples of pseudoautosomal diseases

Answer 25

• Leri-weill dyschondrosteosis syndrome

- Langer mesomelic dysplasia