Nucleus

Question 1

Emery-Dreifuss Muscular Dystrophy

Answer 1

Defect: Mutated Emerin or Lamin A/C!defected nuclear envelope
Mode of Inheritance: X-linked if Emerin; Autosomal dominant in Lamin A/C Mechanism: Defect in lamin assembly/attachment to nuclear envelope causes
fragile nuclear envelope resulting in disruption of nuclear function: aberrant
distribution of chromosomes is altered
Characteristics: Contractures (especially in elbows, ankles, neck), muscle
weakness and atrophy, heart conduction defects and arrhythmias, sudden heart failure Key Words: emerin, contracture, sudden heart failure

Question 2

Dilated Cardiomyopathy

Answer 2

Defect: Lamin A/C defect (RARE CAUSE)
Mode of Inheritance:
Mechanism: Defected lamin causes fragile nuclear lamina and subsequent cell death Characteristics: CHF
Key Words: lamin A/C, CHF

Question 3

Lipodystrophy

Answer 3

Defect: Lamin A/C defect
Mode of Inheritance:
Mechanism: preLamin A interacts with adipocyte TF (impaired adipocyte differentiation)
Characteristics: accumulation of adipose tissue in face and neck, peripheral lipoatrophy with muscle prominence
Key Words: lamin A/C, preLamin A, adipocute accumulation, muscle prominence

Question 4

Hutchinson-Gilford Progeria Syndrome

Answer 4

Defect: Lamin A defect
Mode of Inheritance: Autosomal dominant (sporadic)
Mechanism: Defect in lamin causes fragile nuclear envelope (bleb formation, loss of peripheral heterochromatin, NPC clustering) resulting in progressive nuclear damage
and premature cell death
Characteristics: normal at birth/early infancy but failure to thrive around 18-24 mos, prominent eyes, alopecia, loss of subcutaneous fat, joint stiffness, arteriosclerosis ~5 y/o, 80% die from MI or CHF
Key Words: bleb formation, premature cell death, alopecia, prominent eyes, arteriosclerosi

Question 5

Spinal Muscular Atrophy (Type I,II,III – infantile, intermediate, adult)

Answer 5

Defect: Mutation of SMN protein in gem of nucleus
Mode of Inheritance: Recessive
Mechanism: Mutated SMN causes defective snRNP assembly subsequent
defective pre-mRNA splicing causing loss of motor neurons
Characteristics: sudden onset, rapid progression; muscle weakness and atrophy, hypotonia, dysphagia and feeding difficulties, RTIs
Key Words: SMN in Gems, defected snRNP assembly, hypotonia, *most common genetically related neonatal death