Type II Collagenopathies Flashcards
what genes encode type II collagen
COL2A1, COL2A2
inheritance pattern of type II collagenopathies?
AD in COL2A1
characteristics of inheritance for type II collagenopathies?
locus heterogeneity
phenotypic heterogeneity
three main type II collagenopathies?
Stickler Syndrome (mild)
Kniest Dysplasia (moderate)
Achondrogenesis type II (severe)
clinical features of Stickler
premature osteoarthritis flattened facial profile midline cleft palate ocular myopia retinal detachment hearing loss
inheritance characteristics of stickler?
locus heterogeneity
clinical features of kniest dysplasia?
dwarfing disorder severe retinal degeneration cleft palate scoliosis mobility limitations variability
clinical features of achondrogenesis type II
lethal skeletal dysplasia
lack of bony ossification
very short limbs
mechanism of stickler?
null mutations giving a premature stop codon
haploinsufficieny
mechanism of achondroplasia and Kniest dysplasia
missense mutations that give structurally defective type II collagen
Gly substituted w/ larger AA
dominant negative effect
definitely of dominant negative
abnormal protein interferes with normal protein
what is worse in type II collagenopathies, missense or null?
missense has a more severe phenotype b/c of dominant negative effect
how is a fatal condition?
de novo or germline mosaicism in one parent
what is recurrence risk in parent w/ one affected child?
< 5% even if parent tests negative for disease mutation
