X-Linked Inheritance

Question 1

Hemophilia B

Answer 1

Deficiency of factor IX

Question 2

Clinical features of hemophilia A

Answer 2

Excessive bleeding after minor trauma
Easy bruising
Bleeding into joints, muscles and internal organs

Question 3

Molecular genetics of hemophilia A

Answer 3

Inversion: F8 intron 22

1/3 are new mutations

Question 4

Duchenne muscular dystrophy

Answer 4

Complete absence of dystrophin

Question 5

Becker muscular dystrophy

Answer 5

Decreased amounts of dystrophin

Question 6

Clinical features of muscular dystrophy

Answer 6

Proximal muscle weakness beginning at age 5
Gower movement
Pseudohypertrophy of calf muscles
Wheelchair in early adolescence

Question 7

Molecular genetics of muscular dystrophy

Answer 7

Duchenne: premature termination or frame shift mutation
Becker: in frame mutation
30-50% are new mutations

Question 8

Spinal and bulbar muscular atrophy

Answer 8

Progressive neuromuscular disorder resulting in proximal muscle weakness

Question 9

Clinical features of spinal and bulbar muscular atrophy

Answer 9

Gynecomastia
Testicular atrophy
Reduced fertility

Question 10

Molecular genetics of spinal and bulbar muscular atroph

Answer 10

Trinucleotide repeat (CAG) causing gain of function mutation

Question 11

Clinical features of Rett syndrome

Answer 11

Regression at 6 months of birth
Severe progressive mental impairment with autism
Acquired microcephaly
Loss of purposeful hand movements; hand wringing

Question 12

Molecular genetics of Retts syndrome

Answer 12

Mutations in MECP2 gene

99% are new mutations

Question 13

Fragile X syndrome

Answer 13

Fragility of Xq28 due to folic acid deficiency

Question 14

Molecular genetics of fragile X syndrome

Answer 14

CGG trinucleotide repeat in FMR1

Question 15

Clinical features of fragile X males

Answer 15

Mental retardation
Behavior problems
Long face, prominent forehead, large ears, prominent jaw
Macroorchidism
Mitrovalve prolapse

Question 16

Clinical features of fragile X syndrome females

Answer 16

Less severe mental retardation
Psychiatric problems
Long face, large ears
Mitral valve prolapse

Question 17

Hemophilia A

Answer 17

Deficiency of factor VIII