Lecture 29

Question 1

what are the features of Fragile X Syndrome?

Answer 1

• gene disorder on OMIM 309550, FMR-1
• most common form of inherited mental retardation. + minor physical defects and large testes
• also called martin-bell syndrome
• x chromosome has a characteristic constriction that looks like it could break.
• female symptoms vary considerably more due to x-inactivation
• x linked DOMINANT (males can never pass it to daughters for an unknown reason.

Question 2

what is the sherman paradox?

Answer 2

the penetrance of the mutation varies between families and can change in subsequent generations. Some females pass their fragile x gene and have many affected offspring while others have very little affected offspring.

Question 3

what are the genetic features of Fragile X Syndrome?

Answer 3

• gene disorder on OMIM 309550, FMR-1
• also called martin-bell syndrome
• x chromosome has a characteristic constriction that looks like it could break.
• x linked DOMINANT (males can never pass it to daughters for an unknown reason.
• there is a triplet repeat of CGG in the 5’ untranslated region of the FMR-1 gene. Normal people have 10-100 CGG repeats, while affected people have over 200 CGG repeats often over 800 as a result of a huge expansion. This huge expansion causes hypermethylation of the C’s in these CG regions resulting in inactivation.

Question 4

what is a permutation carrier?

Answer 4

a person with the Fragile X repeat CGG that repeats between 50-100 times.

Question 5

What are the clinical features of myotonic dystrophy?

Answer 5

• Autosomal DOMINANT
• myotonia, progressive muscle weakness an degeneration, normal intelligence, baldness and cataracts.
• unlike fragile x syndrome, has earlier onset of more severe symptoms in successive generations (anticipation)

Question 6

what are the clinical features of Fragile X Syndrome?

Answer 6

• most common form of inherited mental retardation. + minor physical defects and large testes
• female symptoms vary considerably more due to x-inactivation

Question 7

what are the genetic features of myotonic dystrophy?

Answer 7

• OMIM 160900 autosomal DOMINANT
• CTG tandem repeat in the 3’ UTR of the gene that encodes the Dystonia Myotonia Protein Kinase (DM1) which is responsible for phosphorylating other proteins.
• less than 40 repeats is a normal human, 150 repeats has mild symptoms, 500 has muscular dystrophy, 1000 has congenital onset.
• mutation in DM2 gene also gives the same disease

Question 8

what are the clinical features of huntingtons disease?

Answer 8

• neurodegenerative disorder characterized by chorea (greek means “dance”, unconrollable hand a feet movement), rigidity and dementia with death 10-15 years after onset.
• symptoms usually develop in 40s, 50s, and 60s

Question 9

what are the clinical features of huntingtons disease?

Answer 9

• neurodegenerative disorder characterized by chorea

Question 10

what are the genetic features of huntington’s disease?

Answer 10

• under 40 CAG repeats is normal, over 40 has late onset, 120 CAGs can get it as early as 2 years old.

Question 11

what are the clinical features of Kennedy disease?

Answer 11

• early onset non-progressive spinal bulbar muscular atrophy which is a motor neuropathy compatible with long life in affected males.

Question 12

what are the genetic features of Kennedy disease

Answer 12

• an expansion of the CAG triplet in the coding region of the Androgen Receptor Gene (AR).
• 40 or less is normal, same rules as Huntington.q