Disorders Flashcards
What is PMP22 gene?
Peripheral Myelin Protein 22
Duplication of PMP22 gene causes what disorder?
Charcot-Marie-Tooth Type 1A
Deletion of PMP22 causes?
HNPP (Hereditary Neuropathy with liability to pressure palsies).
Where is PMP22 gene located?
17p12
What the the clinical features of Charcot-Marie tooth disease type 1A?
Muscle weakness & atrophy in the extremities (arms, legs, hands or feet).
Some cases: reduced ability to feel cold/ heat or pain!
What are the features of HNPP
Recurrent episodes of sensory & motor neuropathy in a single nerve.
Atrophy & weakness of hands, carpal tunnel syndrome, & pain.
What is gene & chromosome location associated with Rett syndrome?
Xq28, MECP2 Gene
Cause of Retts: 80% mutations or can be large deletions!
What are the features of Rett syndrome?
Neurodevelopmental disorder (almost exclusively in females).
- Arrested development between 6 & 18mths, loss of speech, stereotypical movement of hands, microcephalic, seizures & mental retardation.
What is gene & chromosome location associated with Rett syndrome?
Xq28, MECP2 Gene
Cause of Retts: 80% mutations or can be large deletions!
What are the features of Rett syndrome?
Neurodevelopmental disorder (almost exclusively in females).
- Arrested development between 6 & 18mths, loss of speech, stereotypical movement of hands, microcephalic, seizures & mental retardation.
How can adult males with Rett syndrome exist?
- 47,XXY karyotyping
- Postzygotic MECP2 mutations resulting in somatic mosaicism.
- normal karyotyping but mild MECP2 missense change.
- Dies NOT totally inactive the protein, causing ID in makes but only v.mild cognitive impairment in females.
Name example of X-linked dominant disorder & X-linked recessive?
- X-linked dominant = Rett syndrome
- X-linked recessive = Duchenne muscular dystrophy. (Mutation in dystrophin gene -2/3 inherited from mother). Serum creating kinase levels extremely high in DMD (x10 normal).
Features of DMD: progressive muscle weakness. Impaired motor dev, 50% lower IQ, wheelchair bound by 13.
CARDIOMYOPATHY: after 18 yr. respiratory complication & cardiomyopathy common cause of death. Makes don’t reproduce! - DMD & BMD show complete penetrance in males; penetrance in females depends on XIC & phenotypes can range from unaffected to severe (manifesting heterozygous).
What is main cause of DMD/BMD?
- maj mutations are deletions/duplications of >1 exon
- 65-7o% of DMD & 80-85% BMD.
- 2 deletion hotspots:
80% deletions in Central region (Exxon’s 44-53)
5’ regions (Exons 2-20), 20% deletions.
Treatment: physiotherapist, steroids.
New: Exon skipping: Exondys51 (FDA approval), for DMD amenable to exon 51 skipping! (~13% DMD patients).
Exon skipping: can restore production of dystrophin gene. Skips an exon in RNA to align the remaining exons, making them ‘in-frame’. Now able to translate the RNA into fnt but shorter form of dystrophin, may slow disease progress!
What is location of dystrophin gene?
Xp21
What is Hunter Syndrome (X-linked recessive)?
- Caused by mutations in IDS gene, essential for breakdown of glycosaminogylcans (GAGs).
- Mucopolysaccharides build up in various organs! Age of onset/severity/progression significantly vary among affected males.
- In severe disease: CNS involvement & cardiac disease, usually result in death in 1st/2nd decade of life!
