Autosomal recessive Flashcards
What are the 4 common CFTR mutations?
Phe508Del
Gly551Asp
Gly542*
C.489+1G>T
symptoms of CF?
Severe and chronic lung disease Pancreatic insufficiency Pancreatitis Gastrointestinal complications Meconium illeus CBAVD Fatty stools Malabsorption
Fetal echogenic bowel
Salt loss syndromes
Key facts about CF - gene, carrier frequency, mode of inheritance
CFTR gene
Carrier frequency: 1:25
Autosomal recessive
What is role of CFTR
Cyclic AMP activated chloride channel in plasma membranes if secretory epithelial cells lining lungs, pancreas, gut, vas deferens and sweat ducts
When is 5T analysis needed?
All males with infertility caused by obstructive azoospermia
Patients with bronchiectasis/pancreatitis with only 1 pathogenic variant
Patients with R117H mutation
5 classes of CFTR mutation?
- No synthesis
- premature termination - nonsense/frameshift e.g. Gly542*
- abnormal splicing e.g. c.489+1G>T - block in processing - protein misfolded and defective maturation leads to protein degradation e.g. phe508del
- Block in regulation - defects in channel activation e.g. G551D
- Reduced capacity for CL conductance e.g. R117H&5T
- Other ion channels
Other genes in SMN region?
NAIP, gtf2H2A & SERF1A/B
Symptoms of SMA?
Spinal muscular atrophy
Neuromuscular disorder
Loss of alpha neurons in spinal cord, atrophy (wasting) of limb and trunk muscles
What % of SMA individuals have a deletion?
90-98%
Basics of SMA - gene, carrier freq, location?
SMN
5q11.2-13.3
1:38-1:70
Mostly deletion at least exon 7, some point mutations
Difference SMN1 and SMN2?
2 exotic changes
Smn2 produces 10% full length protein 90% non-functional lacking exon 7
C TO T change which either disrupts enhanced that binds SR protein or create new exon splicing silencer that binds hnRNP proteins.
