Another mutation in the same gene results in a nonfunctional inhibitor of CDK4, a cyclin-dependent kinase that promotes cell division. Mutations that cause the skin condition xeroderma pigmentosum  (XP) also increase melanoma susceptibility. Scattered throughout the genome, these mutations reduce a cells ability to repair DNA. Both CDKN2A and XP mutations are highly penetrant (the chances of a carrier to express the phenotype is high).Familial melanoma  is genetically heterogeneous, and loci for familial melanoma appear on the chromosome arms 1p, 9p and 12q. Multiple genetic events have been related to melanomas pathogenesis (disease development). The multiple tumor suppressor 1 (CDKN2A/MTS1) gene encodes p16INK4a – a low-molecular weight protein inhibitor of cyclin-dependent protein kinases (CDKs) – which has been localised to the p21 region of human chromosome 9. FAMMM is typically characterized by having 50 or more combined moles in addition to a family history of melanoma. It is transmitted autosomal dominantly and mostly associated with the CDKN2A mutations. People who have CDKN2A mutation associated FAMMM have a 38 fold increased risk of pancreatic cancer.Other mutations confer lower risk, but are more common in the population. People with mutations in the MC1R gene are two to four times more likely to develop melanoma than those with two wild-type (typical unaffected type) copies. MC1R mutations are very common, and all red-haired people have a mutated copy.
Heavy chain disease is a form of paraproteinemia and plasma cell dyscrasia that involves the proliferation of cells producing immunoglobulin heavy chains.This disease is characterized by an excessive production of heavy chains that are short and truncated. These heavy chain disease proteins have various deletions, mainly in their amino-terminal part, which causes the heavy chains to lose the ability to form disulfide bonds with the light chains. The defect in the immunoglobulins presumably arises during somatic hypermutation. Deletion of the N-terminal part of the heavy chain disease protein leads to aggregation and signaling of the B cell receptor, presumably due to the loss of the anti-aggregating properties of the light chain. Classification
There are four forms:

alpha chain disease (Seligmanns disease)
gamma chain disease (Franklins disease)
mu chain disease
delta chain disease

IgA/αHCD
The most common type of heavy chain disease is the IgA type, known as αHCD. The most common type of αHCD is the gastrointestinal form (known as immunoproliferative small intestine disease or IPSID), but it has also been reported in the respiratory tract, and other areas of the body. IgG/γHCD
Franklins disease (gamma heavy chain disease)
It is a very rare B-cell lymphoplasma cell proliferative disorder which may be associated with autoimmune diseases and infection is a common characteristic of the disease. It is characterized by lymphadenopathy, fever, anemia, malaise, hepatosplenomegaly, and weakness. The most distinctive symptom is palatal edema, caused by nodal involvement of Waldeyers ring. Diagnosis is made by the demonstration of an anomalous serum M component that reacts with anti-IgG but not anti-light chain reagents.