Autosomal Dominant Inheritance

• Loss of function mutations are associated with haploinsufficiency
• Charcot - Marie - Tooth (CMT 1A) & Achondroplasia have gain of function mutations
• Charcot - Marie - Tooth is associated with a PMP22 duplication
• In familial hypercholesterolemia, higher LDLR = milder phenotype
• Achondroplasia is caused by a gain of function mutation in the FGFR3 gene, leading to overactive signaling and impaired bone growth. 
• Tuberous sclerosis (recurrence risk about 1-2%) & Neurofibromatosis Type 1 (NF1) are examples of germline mosaicism
• 80% of cases of achondroplasia are the result of new mutations (born to unaffected parents)