Desmocollin-3 is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the DSC3 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

Gene

The desmosomal family members are arranged in two clusters on chromosome 18, occupying less than 650 kb combined. Alternative splicing results in two transcript variants encoding distinct isoforms.

Function

Desmocollin-3 is a calcium-dependent glycoprotein

Glycoprotein

Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

 that is a member of the desmocollin

Desmocollin

Desmocollin is a type of cadherin.Specifically, it can refer to one of the following human genes :* DSC1* DSC2* DSC3...

 subfamily of the cadherin

Cadherin

Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...

 superfamily. These desmosomal

Desmosome

A desmosome , also known as macula adherens , is a cell structure specialized for cell-to-cell adhesion...

 family members, along with the desmoglein

Desmoglein

The desmogleins are a family of cadherins consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes that join cells to one another....

s, are found primarily in epithelial cells where they constitute the adhesive proteins of the desmosome cell-cell junction and are required for cell adhesion and desmosome formation. The loss of these components leads to a lack of adhesion and a gain of cellular mobility.

Breast cancer

Through the process of epigenetic silencing

Gene silencing

Gene silencing is a general term describing epigenetic processes of gene regulation. The term gene silencing is generally used to describe the "switching off" of a gene by a mechanism other than genetic modification...

, the expression of the desmocollin 3 protein is down regulated in many breast cancer

Breast cancer

Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

s.

Hereditary hypotrichosis

A consanguineous

Consanguinity

Consanguinity refers to the property of being from the same kinship as another person. In that respect, consanguinity is the quality of being descended from the same ancestor as another person...

 Afghan family in which 3 sisters, 12 to 18 years of age, and their 5-year-old brother displayed features of hereditary hypotrichosis

Hypotrichosis

Hypotrichosis is a condition of abnormal hair patterns - predominantly loss or reduction. It occurs, most frequently, by the growth of vellus hair in areas of the body that normally produce terminal hair. Typically, the individual's hair growth is normal after birth, but shortly thereafter the hair...

, associated with vesicles on the scalp and skin. At birth, scalp hair was present, and after ritual shaving at 1 week of age, scalp hair grew back; however, the hair was fragile and began falling out at 2 to 3 months of age, eventually leaving only sparse hair on the scalp. Vesicles that were less than 1 cm in diameter were observed on the scalp and skin of most of the body, occasionally disappearing but then reappearing; intermittently, the vesicles would burst with a release of fluid, leaving scars on the site that took 3 to 4 months to heal. There were no mucosal vesicles. Upon examination, the affected individuals were nearly devoid of eyebrows, eyelashes, axillary hair, and body hair. Teeth, nails, palms, soles, sweating, and hearing were normal, as was electrocardiography. Serum IgA

Immunoglobulin A

Immunoglobulin A is an antibody that plays a critical role in mucosal immunity. More IgA is produced in mucosal linings than all other types of antibody combined; between three and five grams are secreted into the intestinal lumen each day....

, IgE

Immunoglobulin E

Immunoglobulin E is a class of antibody that has been found only in mammals. IgE is a monomeric antibody with 4 Ig-like domains...

, and IgD

Immunoglobulin D

Immunoglobulin D is an antibody isotype that makes up about 1% of proteins in the plasma membranes of immature B-lymphocytes where it is usually coexpressed with another cell surface antibody called IgM. IgD is also produced in a secreted form that is found in very small amounts in blood serum...

 were measured in 1 individual and showed no change compared to controls. The parents were clinically unaffected. A scalp biopsy of the 18-year-old sister showed slight follicular plugging, mild perivascular and periadnexal inflammatory cell presence, and normal hair follicles. The sebaceous glands appeared morphologically normal and connected to the hair follicles.

Mapping

Genotyping

Genotyping

Genotyping is the process of determining differences in the genetic make-up of an individual by examining the individual's DNA sequence using biological assays and comparing it to another individual's sequence or a reference sequence. It reveals the alleles an individual has inherited from their...

 and linkage analysis

Genetic linkage

Genetic linkage is the tendency of certain loci or alleles to be inherited together. Genetic loci that are physically close to one another on the same chromosome tend to stay together during meiosis, and are thus genetically linked.-Background:...

 of the consanguineous Afghan family resulted in a maximum 2-point load score of 2.68 (theta = 0.0) at markers D18S36 and D18S547. Multipoint analysis generated a maximum load score of 3.30 at marker D18S877. Recombination

Genetic recombination

Genetic recombination is a process by which a molecule of nucleic acid is broken and then joined to a different one. Recombination can occur between similar molecules of DNA, as in homologous recombination, or dissimilar molecules, as in non-homologous end joining. Recombination is a common method...

 events defined an 8.30-cM critical interval on chromosome 18q12.1, flanked by markers D18S66 and D18S1139, containing 30 genes.

Molecular genetics

A a nonsense mutation in the DSC3 gene (600271.0001) mapping to chromosome 18q12.1 was identified in the onsanguineous Afghan family with hypotrichosis and recurrent skin vesicles (613102). The unaffected parents and 3 healthy sibs were heterozygous for the mutation, which was not found in 100 unrelated ethnically matched controls. In affected members of this family with hypotrichosis were homozygous for a 2129T-G transversion in exon 14 of the DSC3 gene, resulting in a leu710-to-ter (L710X) (Ayub et al 2009)substitution at the junction of the transmembrane and the C-terminal cytoplasmic domain, predicted to cause premature termination and nonsense mediated decay of the mRNA or instability of the truncated protein. The unaffected parents and 3 healthy sibs were heterozygous for the mutation, which was not found in 100 unrelated ethnically matched controls.

Further reading