• X-linked recessive
• 1:3500
• age of onset 3-5 years, wheelchair by 12, death in 3rd decade
• Becker MD --> milder form, different mutation
• Loss of dystrophin protein in affected individuals (usually deletion) --> cannot make protein
• Loss of protein due to huge deletions (65% of cases)
• Loss of protein may be due to point mutations (30% of cases) --> must sequence entire gene to find the mutation
• No cure

• protein complex connects cytoskeleton of muscle fibers to surrounding matrix
• longest gene in human
• small amounts within humans (0.1% protein), seen as isoforms in muscles/brain
• makes cytoskeleton protein
• large helical domain with extended n- and c-terminals

• Used to detect deletions rapidly in a large gene
• qualitative test for carrier
• requires multiple primer

• compares controls w/o disease with females who may be carriers
• if female has ~50% of control then she is a carrier

• amplification of multiple targets using only one primer
• females show 50% of 1, 2, and 3 below
• probe specificity made against all targets

1. Probe hybridizes to sequence
2. Probe ligation of sequence
3. Use fluorescent-labeled primers to amplify probes
4. Separation and Quantification (detect fluorescence)

• Mother tests as normal but child still inherits condition due to mosaicism (15% chance of inheritance)
• Cannot be predicted

• Both possess same types and sizes of the deletions
• In DMD the reading frame is shifted --> may get back into frame with exon skipping (cover up exons with small pieces of DNA and encourage the reading frame to skip over the exon --> leads to symptoms more like BMD)
• In BMD the reading frame is shifted

• Utrophin --> similar to dystrophin but normally found in neurons (inject into muscle cells)
• Microdystrophin --> vector which seeks to reinstate original reading frame and give BMD phenotype
• Exon skipping anti-sense therapy

• 1:2500
• autosomal recessive
• loss-of-function mutations
• pancreatic insufficiency and obstructive pulmonary disease
• multisystemic due to defective electrolyte transport in epithelium
• Survival age = 40 --> much higher than it used to be
• Infertile males, dec fertility in females
• Mutations in CFTR gene on chrome 7 --> 2-3 bp deletions
• Classes 1, 2, 3 show severe phenotypes with 3 the only one that has protein synthesis
• Every state has Newborn screens for CF

• chest percussions to clear secretions
• control infections with antibiotics
• nutritional improvement

• cystic fibrosis transmembrane conductance regulator protein
• chloride channel transporter
• ABC transporter sub-family C --> loss-of-function results in abnormal Cl^-, Na⁺, H₂O transport
• R117H CF mutation found on 5T allele

• 95% of CF males infertile due to vas deferens absence
• 70% of males with CBAVD have one CF mutation --> no lung disease

• Not detectable at birth
• major health problem
• available treatment
• cost effective
• reliable methods

CF Screens

• early nutritional support
• reduced hospitalization
• improved survival
• reduced expense/anxiety

• Clinically significant disorder with no effective treatment
• high risk population
• available genetic counseling
• accurate/inexpensive tests
• reproductive options available