ALLELIC DISORDERS

 Different diseases phenotypes caused by mutations of the same gene.

 Same gene can underlie different diseases in different ways.
 A pair of allelic disorders may result from mutations in different parts of the gene:
a. Localized (single-based change)
b. Catastrophic (missing gene)
c. Alter the protein in ways that affect its interactions with other proteins.

 Allelic disorders may arise from a mutation that affects a protein that is used in different
tissues.

Example:

Mutations in B3GALT6 cause allelic disorders: (a) spondyloepimetaphyseal dysplasia

with joint laxity, type 1 (SEMD-JL1); (b) Ehlers- Danlos syndrome
progeroid type.

a.
 b.

Gene Function Associated Diseases

ATP7A Copper transport
DMD Dystrophin muscle protein
FBN1 Encodes fibrillin-1, which
forms tiny fibrils outside cells;
a connective tissue protein
FGFR3 Fibroblast growth factor
GBA Glucocerebrosidase
PSEN1 Presenilin 1 (enzyme part that
trims membrane proteins)
Menkes (“kinky hair”)
disease; peripheral neuropathy
DMD Dystrophin muscle
protein Duchenne and Becker
muscular dystrophy
Duchenne and Becker
muscular dystrophy
Marfan syndrome; stiff skin
syndrome (scleroderma)
2 types of dwarfs
Gaucher disease;
Parkinson disease
Acne inversa;
Alzheimer disease

RET Oncogene (causes cancer) Multiple endocrineneoplasia;

Hirschsprung disease
TRPV4 Calcium channel Peripheral neuropathy;
spinal muscular atrophy