Genetic Abnormalities in MSK Disease

Question 1

Hereditary exostoses (osteochondromas)

Answer 1

LOF mutation in EXT1 or EXT2

Question 2

Chondromas

Answer 2

IDH1 or IDH2

Question 3

Osteosarcomas

Answer 3

RB, TP53, INK4a, MDM2, CDK4

Question 4

Chondrosarcoma

Answer 4

DNA methylation of CDKN2A

Question 5

Ewing Sarcoma Family Tumors

Answer 5

(11;22) translocation → fusion of EWS to FLI1

Question 6

Osteogenesis imperfecta

Answer 6

mutations in type I collagen

Question 7

Achondroplasia

Answer 7

GOF mutation in FGFR3

Question 8

Osteopetrosis

Answer 8

LOF mutation in RANKL (AD)
LPR5 mutation
CA2 mutation
CLCN7 mutation

Question 9

Brachydactyly

Answer 9

HOXD13 txn factor

Question 10

Campomelic dysplasia

Answer 10

SOX9 txn factor

Question 11

Cleidocranial dysplasia

Answer 11

RUNX2 txn factor

Question 12

Holt-Oram syndrome

Answer 12

TBX5 txn factor

Question 13

Nail-Patella syndrome

Answer 13

LMX1B txn factor

Question 14

Waardenburg syndrome

Answer 14

PAX3 txn factor

Question 15

Achondrogenesis type II

Answer 15

COL2A1 (type II collagen)

Question 16

Metaphyseal dysplasia

Answer 16

COL10A1 (type X collagen)

Question 17

Thanatophoric dysplasia

Answer 17

GOF in HFGF43

Question 18

Fibrous dysplasia/McCune Albright

Answer 18

GOF in GNAS1

Question 19

Aneurysmal bone cyst

Answer 19

17p13 rearrangement → USP6 ↑

Question 20

Paget disease of bone

Answer 20

SQSTM1