Trinucleotide Repeat Expansion Disorders Flashcards Preview

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Flashcards in Trinucleotide Repeat Expansion Disorders Deck (24):
0

What are characteristics of Trinucleotide repeat expansions?

- expansions can occur in either coding or non-coding regions of a gene
- expansion sites are sometimes associated with hypermethylated regions of the genome and the ability of the sequence to form stable hairpins, perhaps leading to faulty DNA replication, recombination and repair

1

What are examples of mechanisms for Trinucleotide repeat expansions?

- mechanisms for Trinucleotide repeat expansions: slippage of DNA polymerase during strand replication, faulty DNA mismatch repair, uneven crossing over of homologous regions of Trinucleotide repeats, mistakes during transcription-coupled DNA repair

2

What Trinucleotide repeat expansion disorder is caused by triplet repeat expansion of CGG. The higher the CGG the higher the MR this is called anticipation.

Fragile X syndrome

3

What Trinucleotide repeat expansion disorder has a recurrence risk of 1/2000

Fragile X Syndrome

4

What Trinucleotide repeat expansion disorder has the following phenotype:
- long narrow face, prominent ears and jaw and forehead, enlarged testicles, mental impairment, attention deficit and hyperactivity, motor delays?

Fragile X syndrome

5

What Trinucleotide repeat expansion disorder is X-linked dominant. Male can be a carrier. Female heterozygous for triplet nucleotide expansions often develop problems such as ovarian failure and ataxia?

Fragile X syndrome

6

What Trinucleotide repeat expansion disorder is caused by CAG repeats located in exon 1 of the HD gene. HD gene is ITI5 located at 4p16.3 and encodes the Huntington protein: regulates intracellular transport, functions in transcription by shuttling transcription factors in and out of the nucleus, required for normal embryonic development and neurogenesis

Huntington Disease

7

What Trinucleotide repeat expansion disorder has the following phenotype:
- chorea, ataxia, dysarthria

Huntington's disease

8

Southern blot is used to obtain exact lengths for long CAG repeats in what Trinucleotide repeat expansion disorder?

Huntington's disease

9

What Trinucleotide repeat expansion disorder is autosomal dominant. HD gene expressed in many tissues, but especially high in the testes and brain. Expansion of CAG region results in aggregation of the mutant protein into inclusion bodies. Variable expressivity?

Huntington's Disease

10

What Trinucleotide repeat expansion disorder is caused by CTG repeat on DMPK gene on c19: affects all skeletal muscle?

Myotonic Dystrophy

11

What Trinucleotide repeat expansion disorder has the following phenotype:
- muscles are slow or unable to relax, problems walking, cardiac conduction defects, ptosis, dysphagia, respiratory insufficiency, cataracts, club foot, pulmonary hypertension, intellectual disability, delayed development

Myotonic Dystrophy

12

What Trinucleotide repeat expansion disorder is 100% fatal?

Myotonic Dystrophy

13

What Trinucleotide repeat expansion disorders are autosomal dominant?

Huntington's disease
Myotonic Dystrophy
Oculopharyngeal Muscular Dystrophy (OPMD)

14

What Trinucleotide repeat expansion disorder is caused by a triplet repeat GAA in the 1st intron at FXN gene on c9 which encodes frataxin to remove iron in the cytoplasm around the mitochondria. Iron build-up (transcriptional repression) causes free radical damage to the mitochondrial membrane, especially affecting nerve and muscle cells

Friedreich Ataxia

15

What Trinucleotide repeat expansion disorder has a 1/50,000 recurrence risk (25% in USA)

Freidreich Ataxia

16

What Trinucleotide repeat expansion disorder has the following phenotype:
- muscle weakness in the arms and legs, loss of coordination, vision impairment, hearing impairment, slurred speech, scoliosis, pes cavus, diabetes, heart disorders?

Freidreich Ataxia

17

In what Trinucleotide repeat expansion disorder do symptoms begin at 5-15 y/o. Treatment is supportive: scoliosis surgery, cardiac meds, physical therapy?

Freidreich Ataxia

18

What Trinucleotide repeat expansion disorders are autosomal recessive?

Freidreich Ataxia

19

What Trinucleotide repeat expansion disorder is caused by triplet repeat GCG in PABPN1 gene on c14=hyper aggregation=toxic. Protein required for termination of Poly(A) tail synthesis at 250-300 nt?

Oculopharyngeal Muscular Dystrophy (OPMD)

20

What Trinucleotide repeat expansion disorder has the following phenotype:
- ptosis, dysphagia, dysphonia, facial weakness, weakness in proximal limbs, limited mobility

Oculopharyngeal Muscular Dystrophy (OPMD)

21

In what Trinucleotide repeat expansion disorder is treatment supportive, surgical correction of ptosis, diet adjustments?

Oculopharyngeal Muscular Dystrophy (OPMD)

22

What Trinucleotide repeat expansion disorder is autosomal dominant, doesn't shorten life span, fully penetrant?

Oculopharyngeal Muscular Dystrophy (OPMD)

23

What are examples of Trinucleotide repeat expansion disorders?

Fragile X syndrome
Huntington 's disease
Myotonic Dystrophy
Freidreich Atrasia
Oculopharyngeal Muscular Dystrophy (OPMD)