Collagen defects

Question 1

Osteogenesis Imperfecta

Answer 1

Bone=type 1 coll embedded in CaPh matrix
Muts of type 1 coll, precoll alpha1 chain genes
Most clinical severe phenotypes form substitute of inverted glycine
3x helix forms C to N term: gly mutations near C term = more deleterous; N term permits substantial 3x helix formation
Ranged severity: perinatal death - mild dispostion to fractures
Clin= skl defects, fractures, blue sclera

Question 2

OI types

Answer 2

1. mild, blue scl and bone fragile
2. lethal, blue scl; severe fragility; no mineralization; skl deformation
3. Deform, bl/wh sclera; dentinogenesis imperfecta; fragile; short
4. Mild deform, norm scl; dent imp; short; frag-moderate

Question 3

Ehlers Danlos Syndrome

Answer 3

CT weak - not enough tensile str - hyper skin and joints

Internal complications - ruptured colon, large arts, varricose veins, eccymoses

Question 4

ED syn types

Answer 4

1. coll1/5: joints and skin
2. Coll 3: vascular type: arteriol, intestinal, uterine rupture, bruise, thin skin, varricose veins
3. Muts lysyl hydroxylase - coll no struc stability. Occular fragility: retinal hemorrhage and detach, corneal rupture, Kyphoscoliosis
4. Procoll 1 - coll 1 - joints

Question 5

Alpart Signal

Answer 5

Common inherited cause of kidney failure

Mut alpha5 chain of type 4 collagen (BL) - Nephrititis and deaf: Haematuria, Proteinuria, HTN

Question 6

Good Posture syndrome

Answer 6

AutoImmune (20+ males). Antibodies to coll 4 (alpha3 chain) - inflamm destruction of BM in kidney glom and lung alveoli: Haemoptysis and glomeruolomphritis with progressive renal fail

Question 7

Epidermolysis Bullosa forms

Answer 7

1. EBS (EB simplex): mut keratin 5/14
   2, Jx’l EB - mut laminin, integrins, hemides
2. Dys EB - mut coll 7
   Butterfly children with extremely fragile skin, friction=blister

Question 8

Dystrophic EB

Answer 8

Mut coll 7: absence of anchoring filaments, blistering causes syndactyly

Question 9

FGFR3 Mut: Achondroplasia

Answer 9

Most common dwarfism, 1/100k, <4ft, constituitive expression FGFR3 in chondrocytes - restricts chondrocyte proliferation - excessive bone growth inhib therefore inhibits cartilage growth and coll 2
Stops act of RTK FGFR3 = dwarfism