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Cystic fibrosis Case studies

Cystic fibrosis Case studies. Danielle Crompton. Introduction. Autosomal recessive disorder. Carrier frequency of 1 in 25. Average median survival age is 33 years. Mutations in the CFTR gene.

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Cystic fibrosis Case studies

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  1. Cystic fibrosis Case studies Danielle Crompton

  2. Introduction • Autosomal recessive disorder. • Carrier frequency of 1 in 25. • Average median survival age is 33 years. • Mutations in the CFTR gene. • Clinical features range from mild to severe and include pancreatic insufficiency, susceptibility to lung damage, disrupted liver function and infertility in males. • There are currently 1547 mutations listed in the CFTR mutation database. • Mutation Classes - good correlation with a mutations severity and often provides a rationale for their phenotypic consequences.

  3. R117H and poly T • Poly T polymorphisms in intron 8 consists of three alleles, in which there can be 5T’s, 7T’s or 9T’s. • 5T at this locus associated with high levels of exon 9 skipping, whereas those with 7T or 9T have successfully lower levels of skipping causing differences in phenotypic expression of the disease state. • R117H is a missense mutation whose effect is modulated by the length of the poly T tract

  4. R117H R117H R117H 7T 5T 5T 5T CF (PS) CF (PS) CBAVD Asymptomatic Mild CF CBAVD Asymptomatic Mild CF CBAVD Asymptomatic Mild CF 1 2 Severe CFTR mutation 3 4

  5. Case study 1 - MM

  6. 1 2 3 4 5 6 Photo of electrophoresis gel for ARMS29 PCR analysis. Lane 1 – 50bp ladder, lanes 2-5 ARMS29 PCR products, lane 6 – 50bp ladder. DF508(N) 160bp

  7. Report writing • Mother of MM is in fact a carrier of the R117H mutation not the delta F508 mutation as stated on the referral form. • MM does not have the R117H mutation.

  8. ? R117H 7T 7T MM Does MMs’ mother have a rare mutation that she has passed on to MM?

  9. R117H DF508 ? R117H 7T 7T 7T MM Mothers’ sister is affected with CF and has the R117H and the delta F508 mutations.

  10. ? R117H DF508 ?1/161 R117H DF508 R117H 7T 7T 7T MM MM is not affected with CF

  11. Case study 2 - BB • BBs’ parents had previously been tested and his mother was found to be negative for the common mutations. • Father was found to be a carrier of the R117H mutation. • Father heterozygous for the 5T/7T allele.

  12. R117H R117H 7T 5T 5T 7T CF (PS) – severe mutation CBAVD Asymptomatic Mild CF

  13. Photo of electrophoresis gel for ARMS29 PCR analysis. Lane 1 – 50bp ladder, lanes 2-5 ARMS29 PCR products, lane 6 – 50bp ladder. DF508(N) 160bp Highly unlikely that BB has CF although we cannot exclude the possibility that rare CFTR gene mutations may be present.

  14. Conclusions • Importance of family history and knowing which mutations are present within the family when predicting a patients genotype. • It is vital to consider different combinations of genes and their varying phenotypic effects.

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