Brittle bone disease

Question 1

What is brittle bone disease also known as?

Answer 1

Osteogenesis imperfecta

Question 2

What is the main feature of osteogenesis imperfecta?

Answer 2

Repeated fracture of long bones and malformed bones

Question 3

What causes osteogenesis imperfecta?

Answer 3

It is a genetic disorder mostly inherited as autosomal dominant
Can be caused by a whole range of genetic disorders

Question 4

What is an example of a genetic disorder which can cause osteogenesis imperfecta?

Answer 4

Point mutation (G replaced by T) in gene for collagen type I. This results in glycine residue switched for cysteine.
Cysteine is a larger AA and causes a kink in the normally straight triple helix- causes defective structural assembly 
Cystine also contains reactive sulphydryl group so inappropriate disulphide bonds can form between two a1(I) chains in helix

Question 5

How is a patient who is heterozygous for osteogenesis imperfecta affected?

Answer 5

Only some of their a1(I) chains will be abnormal while other allele is making the normal version

Question 6

What other parts of the body can be affected by osteogenesis imperfecta?

Answer 6

Eyes, teeth, skin, ears

Question 7

What does the abnormal collagen lead to?

Answer 7

Leads to defects in mineralisation process so patients has skeletal abnormalities and generally weak bones

Question 8

How can a patient be diagnosed with osteogenesis imperfecta?

Answer 8

Study of collagen proteins using electrolysis

Question 9

How would a foetus be tested for osteogenesis imperfecta?

Answer 9

1. Genetic screening of foetal DNA obtained by chronic villus sampling or amniocentesis and amplified by PCR
2. Use of probes which are complimentary to part of DNA sequence where mutation is known to occur- probe will only bind to DNA if it has complimentary sequence

Question 10

What is the effect of mutations in different types of collagen?

Answer 10

Type I: insufficient quantities of collages

Type II, III, IV: abnormal protein with altered structure