Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CMBM 3 > Single Gene Disorders > Flashcards

Single Gene Disorders Flashcards

1
Q

Polygenic disorders include:

A
  • multiple gene alterations establish susceptibility
  • environmental triggers induce active disease
  • common diseases have no simple pattern of inheritance and have multiple contributing factors
    EX) diabetes
    hypertension
    cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What traits are involved in Single-Gene disorders?

A
  • gene alteration results in disease
  • NO environmental influences
  • Rare events (although collectively common)
    Ex) Huntington Chorea
    Myotonic Dystrophy
    Cystic Fibrosis
    Neurofibromatosis (NF)
    Marfan Syndrome (MFS)
    Duchenne Muscular Dystrophy (DMD)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Genetic disorders impact what percent of overall admissions cases? and end-of-life care admission to LTC facility?

A

50%
60%

Genetic disorders have huge impact on our society.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What can be positive from a deleterious gene?

A

confer and advantage in a heterozygous state

ex) sickle cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

List the inheritance patterns for single gene disorders.

A 
Autosomal Dominant
Autosomal Recessive (most cases)
X-linked dominant
X-linked recessive
Y-linked
Mitochondrial
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is a characteristic of autosomal dominant?

A

appears in every generation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is an example of an autosomal dominant single-gene disorder?

A

Hereditary Motor & Sensory Neuropathy (HMSN)
Neurofibromatosis (NF)
Marfan Syndrome (MFS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What gene is duplicated in Hereditary Motor & Sensory Neuropathy (HMSN) ? result?

A

Periperal myelin protein - PMP-22 (17p) is duplicated and leads to arrests of Schwann cell division

  • interrupts myelin stability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How does Hereditary Motor & Sensory Neuropathy (HMSN) present?

A

slowly progressing distal muscle weakness and wasting

Onset 10-30 years

  • spread to upper limbs and tremors evident
  • foot has high arch and toes curled (hammer toe)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What gene is mutated (can be deletion, insertion, duplications, point mutations) in Neurofibromatosis (NF)? result?

A

neurofibromin (NF1) gene on 17q»truncation to complete absence

  • downregulated Ras acivity through GTPase action (tumor suppressor gene)
  • café au lait macules

-50% of new cases due to new mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are some of the clinical diagnostic criteria for NF1?

A
  • 6 or more cage au lait macules over 5mm (15mm in postpubertal)
  • 2 or more neurofibromas or 1 plexiform neurofibroma
  • optic glioma
  • 2 or more Lisch nodules (iris hamartomas)
  • distinctive osseous lesions
  • 1st degree relative with NF
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are some problems related to NF1?

A
  • nonverbal learning disorder (1/3 of cases)
  • epilepsy
  • CNS tumor
  • scoliosis

**onset by 5 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How is NF1 definitively diagnosed?

A

Gene testing
- only certain labs

**FYI University of Alabama (UAB) are leaders in NF1 testing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What percent of patients over age 8 who carry the NF1 gene have detectable Lisch Nodules on slit-lamp ophthalmologic examination?

A

95%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What gene is mutated (missense with dominant-negative effect) in Marfan Syndrome? result?

A

Type 1 fibrillin (FBN1) (15q21)

  • results in weakened elasticity of ECM
  • cannot retain TGF-b
  • promotes inflammation at sites consistent with MFS symptoms
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What symptoms are a result of MFS?

A
  • tall, reduced supper and lower segment body ratio
  • scoliosis
  • long limbs
  • cardiovascular abnormalities
  • aortic aneurysm is life threatening
17
Q

List the symptoms that are part of the Ghent criteria in MFS?

A

MINIMUM OF TWO MAJOR Criteria plus 3rd organ system**

Skeletal (upper lower ratio >1.05, hypermobility, pes planus)
Ocular (ectopia lentis)
Cardiovascular (dilation/disection of ascending aorta)
Pulmonary (no major, minor - spontaneous pneumothorax)
Skin/Connective tissue
Dura (lumbosacral dural extasia)
Family history (**if applicable, ONE MAJOR criteria plus involvement of second organ system)

18
Q

How would you get a definitive diagnosis of MFS?

A

Mutational analysis will detect 70-93%.
- false positives and negatives
Hence clinical evaluation is important.

**Should also be screened for homocystinuria (treatable IEM of homocysteine metabolism with diet & 50% respond to B6)

19
Q

What is a characteristic of x-linked single-gene disorders?

A

Mothers can only transmit disease to sons.

Daughters can be carriers.

20
Q

What is the average age of onset for Duchenne Muscular Dystrophy (DMD)?

A

3-5 years old

21
Q

What are the symptoms of DMD?

A
  • progressively muscle weakness
  • awkward and clumsy walking on tiptoes
  • most unable to walk by 10
  • mild to moderate intellectual disability; avg 83
22
Q

What gene is deleted in DMD?

A

dystrophin Xp21.1

23
Q

What is dystrophin responsible for? result?

A
  • connection of muscle fibers to the ECM
  • absence of dystrophin results in excess calcium penetrating the sarcolemma (cell membrane)
  • complex cascade results in cell death
  • muscle fibers undergo necrosis and replaced with adipose and connective tissue
24
Q

What treatment is available for DMD and MFS? mechanism of action?

A

Losartan

  • blocks TGF-beta which is too active in MFS patients
  • allowed aorta to develop normally
25
Q

List some X-linked single-gene disorders.

A

Duchenne Muscular Dystrophy (DMD)
Fragile X
Rett’s Syndrome (X-linked dominant)

26
Q

What is the most common cause of inherited learning disability?

A

Fragile X

27
Q

What genetic mutation occurs as a result of Fragile X?

A
  • site on telomeric end of X chromosome susceptible to breakage
  • increase in size of 5’ untranslated region of CGG repeats of FMR-1 gene

> 200 repeats = full mutation

28
Q

What are some clinical features of Fragile X?

A 
autistic phenotype
hyperactive
high forehead
large ears
prominent jaw
learning difficulties
29
Q

What X-linked dominant single-gene disorder affects 1 in 10,000 females?

A

Rett’s Syndrome

*does occur in males

30
Q

How many mutations are de novo in Rett’s?

A

99% - only mutated in that individual

31
Q

When does Rett’s syndrome appear?

A

around 6-18 months

  • decelerated head growth and development
  • loss of acquired skills (speech, motor)
32
Q

Where is the gene mutation for Rett’s syndrome? results?

A

MECP2 gene of X chromosome

  • assumed to be responsible for global gene silencing
  • maintains normal neuronal interactions
  • mutation causes inappropriate gene activation
33
Q

What are the clinical features of Rett’s syndrome?

A
  • microcephaly - will see cortical and cerebellar atrophy
  • autistic phenotypes - hand movements, regression neurological and social skills
  • disease is spectrum from mildly altered speech to severe (unable to walk or interact)
  • Males have severe encephalopathy to adult mental retardation

CMBM 3 (28 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions