Genetic Disorders Flashcards

1
Q

Threshold effect in mitochondrial disease:

A

The vulnerability of each tissue to express disease based on the number of mutant mitochondrial DNA.
(The proportion of normal and abnormal mitchondria can change from tissue to tissue in the same body.)

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2
Q

Heteroplasmy

A

Presence of mixture of mutant and normal mitochondrial DNA.

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3
Q

Charcot-Marie-Tooth (CMT):

A

Slowly progressive peripheral neuropathy which can cause weakness and loss of sensation in the extremities.
Affect feet and hands more than proximal legs and arms.
Structural changes to feet, balance problems, pain and numbness in the hands and feet, decreased fine-motor skills in the hands, difficulty walking and increased fatigue.
>70 genetic causes of CMT: genetic heterogeneity

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4
Q

Most common type of CMT:

A

CMT type 1 is more common than CMT2 or other forms of CMT. CMT1A is the most common sub-type of CMT: 70-80% of CMT1
CMT1 is demyelinating –> slow nerve conduction.

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5
Q

CMT1A is caused by:

A

Duplication of Peripheral Myelin Protein 22 (PMP22) gene which is located on chromosome 17. This is a protein that is essential for the function of the myelin.

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6
Q

CMT1A inheritance:

A

Autosomal dominant

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7
Q

Myotonic Dystrophy (Type 1) (DM1)

A

The word “myotonic” refers to the inability to relax muscles.
The word “dystrophy” refers to progressive muscle weakness and wasting, which is also a symptom of DM1. The muscles of the arms, hands, legs and feet are often affected. Muscle weakness in the feet and legs may lead to difficulty walking. The muscles of the face and neck may also weaken.
DM1 can also cause heart problems, cataracts, sleep apnea, digestive problems, gallstones and diabetes.

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8
Q

Genetic mutation in DM1:

A

DMPK gene mutation on chromosome 19. CTG triplet repeat. 50 will have DM1. 36-49 wont get DM1 but will pass and expansion occurs. Usually from mother not father: Maternal Anticipation Greater # –> earlier onset and more sever.

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9
Q

Spinocerebellar Ataxias (SCAs).

A

> 35 SCA mutations on diff genes.

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10
Q

Huntington’s genetics:

A

Trinucleotide repeat retion “CAG” can expand and contract. Paternal anticipation.

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11
Q

Spinal Muscular Atrophy (SMA)

A

Inherited, causes progressive problems with motor neuron in anterior horn cells. Muscle weakness and muscle loss; worse in legs than arms.

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12
Q

Types of SMA:

A

SMA Type 1: most severe, affects infants

SMA Type 2: children

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13
Q

Genetics of SMA:

A

On chromosome 5; survival motor neuron 1 gene (SMN1). Deletion of part of SMN1 gene. Allelic heterogeneity due to SMN2.
Autosomal recessivve.

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14
Q

ALS genetics

A

AD with incomplete penetrance.

Hexanucleotide repeat with expansion leads to disease: GGGGCC.

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15
Q

Lysosomal Storage Diseases - 3 examples:

A

Pompe
Gaucher
Fabry Disease

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16
Q

Lysosomal Storage Diseases genetics:

A

For X-linked forms symptoms in females range: skewed X-inactivation.

17
Q

Neurofibromatosis Type NF1:

A

Symptoms:

  1. cafe-au-lait (CALS) at least 6.
  2. freckling in armpit (axillary) and groin (inguinal) region.
  3. Lisch nodules - spots in colored parts of the iris.
  4. Neurofibromas - most common tumor in NF1; benign, on skin, or in body (plexiform neurofibroma)-Often during puberty.
  5. If severe: scoliosis, long bone defects, HTN, cancer. Only 15% have serious medical problems.
  6. 50% inherited, rest are de novo muts.