LAMB3 gene…..Location

Cytogenetic Location      :      1q32

Molecular Location         :      base pairs 209,788,214 to 209,825,819 on chromosome 1

The LAMB3 gene is located on the long (q) arm of chromosome 1 at position 32, precisely, the LAMB3 gene is located from base pair 209,788,214 to base pair 209,825,819 on chromosome 1.

LAMB3 gene…..Official Name

Official Name               :      Laminin, beta 3

Official Symbol             :      LAMB3

The LAMB3 gene is also known by other names…..

 @   BM600-125KDA

 @   FLJ99565

 @   kalinin-140kDa

 @   kalinin B1 chain

 @   LAM5, beta-3 subunit

 @   LAMB3_HUMAN

 @   laminin 5, beta-3 subunit

 @   laminin B1k chain

 @   laminin B3

 @   laminin, beta-3

 @   laminin, beta 3 precursor

 @   laminin S B3 chain

 @   LAMNB1

 @   nicein-125kDa

LAMA3 gene cause JEB

How LAMA3 gene cause Junctional Epidermolysis Bullosa?

Mutation in LAMA3 gene causes Junctional Epidermolysis Bullosa [JEB]. More than 30 mutations in the LAMA3 gene have been identified in people with junctional epidermolysis bullosa (JEB). The more severe form of the disease, known as ‘Herlitz JEB’, usually results from mutations which severely disrupt the production of functional ‘laminin 332’. Most of these mutations lead to a premature stop signal in the instructions for making the alpha (α) subunit of laminin 332, which prevents the assembly of this protein. Without laminin 332 the epidermis is weakly connected to the underlying layers of skin. Friction or any minor trauma (such as rubbing or scratching) can cause the skin layers to separate, leading to the formation of blisters. Infants with Herlitz JEB develop widespread blistering that causes life-threatening complications.

Other LAMA3 gene mutations cause the milder form of junctional epidermolysis bullosa, ‘non-Herlitz JEB’. Some of these mutations alter single protein building blocks (amino acids) in the alpha (α) subunit of laminin 332. Others add or delete a small number of amino acids in the alpha (α) subunit or change the way the gene's instructions are used to make the subunit. The genetic changes responsible for non-Herlitz JEB usually lead to the production of a laminin 332 protein which retains some of its function. Affected individuals experience blistering, but it may be limited to the hands, feet, knees, and elbows and often improves after the newborn period.

Source: www.ghr.nlm.nih.gov  

LAMA3 gene....Function

Function of the LAMA3 gene

The LAMA3 gene provides instructions for making one protein subunit — ‘laminin 332’ (formerly known as laminin 5). Laminin 332 is made up of 3 subunits — called alpha (α), beta (β) and gamma (g). The LAMB3 gene carries instructions for the beta (β) subunit; the alpha (α) and gamma (g) subunits are produced from other genes.

Laminins are a group of proteins which regulate cell growth, cell movement (motility) and the attachment of cells to one another (adhesion). They are also involved in the formation and organization of basement membranes — which are thin, sheet-like structures — separate and support cells in many tissues. 

Laminin 332 has an important role in the basement membrane which underlies the top layer of skin (the epidermis). As we discussed earlier basement membrane gives strength & resiliency to the skin and creates an additional barrier between the body and its surrounding environment. 

Source: www.intechopen.com/source/html/42518/media/image1.jpeg 

Laminin 332 is a major component of anchoring filaments which connect the two layers of the basement membrane and help hold the skin together.

Studies suggest that laminin 332 also has several other functions. This protein appears to be important for wound healing. Additionally, researchers have proposed roles for laminin 332 in the clear outer covering of the eye (the cornea) and in the development of tooth enamel.

Source: www.ghr.nlm.nih.gov  

LAMA3 gene.....Location

Location…..

Cytogenetic Location      : 18q11.2

Molecular Location        : base pairs 21,269,561-21,535,029 on chromosome 18

The LAMA3 gene is located on the long (q) arm of chromosome 18 at position 11.2, precisely, the LAMA3 gene is located from base pair 21,269,561 to base pair 21,535,029 on chromosome 18.

LAMA3 gene.....Official Name

Official Name               :      Laminin, alpha 3

Official Symbol             :      LAMA3 

The LAMA3 gene is also known by other names…..

   @   BM600

   @   BM600-150kDa

   @   BM600 150kD subunit

   @   E170

   @   epiligrin

   @   epiligrin 170 kda subunit

   @   epiligrin alpha 3 subunit

   @   kalinin-165kDa

   @   kalinin 165kD subunit

   @   LAM5, alpha-3 subunit

   @   lama3a

   @   LAMA3_HUMAN

   @   laminin-5 alpha 3 chain

   @   laminin 5, alpha-3 subunit

   @   laminin A3

   @   laminin alpha 3

   @   laminin alpha 3 subunit

   @   LAMNA

   @   LOCS

   @   nicein-150kDa

   @   nicein 150kD subunit

The Genes....[JEB]

What genes are related to Junctional Epidermolysis Bullosa?

Junctional Epidermolysis Bullosa [JEB] is caused due to the mutations in the LAMA3, LAMB3, LAMC2 and COL17A1 genes. Mutations in each of these genes can cause Herlitz JEB or non-Herlitz JEB. LAMB3 gene mutations are the most common causing almost 70% of all cases of JEB.

Each of the LAMA3, LAMB3 and LAMC2 gene provides instructions for making one part (subunit) of a protein called ‘Laminin 332’. This protein plays an important role in strengthening and stabilizing the skin by helping the top layer of skin (the epidermis) to attach with the underlying layers. Mutations in any of the three ‘Laminin 332’ genes lead to the production of a defective or non-functional version of this protein. Without functional laminin 332, cells in the epidermis become fragile and easily damaged. Friction or other minor trauma can cause the skin layers to separate, causing the formation of blisters.

The COL17A1 gene provides instructions for making a protein which used to assemble type ‘XVII collagen’. Collagen provides structure and strength to connective tissues such as skin, tendons and ligaments throughout the body. Type XVII collagen helps the epidermis to attach with underlying layers of skin, making the skin strong and flexible. Mutations in the COL17A1 gene prevent the normal formation of collagen XVII — as a result, the skin become less resistant to friction which leads to the formation of blisters due to minor trauma. Most COL17A1 gene mutations cause non-Herlitz JEB, although a few individuals with mutations in this gene have had the more severe Herlitz JEB.

Prevalence....[JEB]

How common is Junctional Epidermolysis Bullosa [JEB]?

Both types of JEB are rare, affecting less than 1 per million people in the United States.

Genetics.....[JEB]

Junctional Epidermolysis Bullosa [JEB].....

Junctional epidermolysis bullosa (JEB) is one of the major forms of Epidermolysis Bullosa.

Junctional Epidermolysis Bullosa [JEB] can be classified into 2 main types: ‘Herlitz JEB’ and ‘non-Herlitz JEB’. Although the types differ in severity but their features overlap significantly—which is caused by mutations in the same genes.

Herlitz JEB is the more severe form of JEB. From birth or early infancy the baby has blistering over large regions of the body. Blistering also affects the mucous membranes such as the moist lining of the mouth and digestive tract which makes eating and swallowing difficult which in turn creates problems in digestion. As a result many affected children have chronic malnutrition and slow growth. The extensive blistering leads to scarring and the formation of red, bumpy patches called ‘granulation tissue’. Granulation tissue bleeds easily and profusely, making affected infants susceptible to serious infections and loss of necessary proteins, minerals, and fluids. Additionally, a build-up of granulation tissue in the airway can lead to a weak, hoarse cry and difficulty breathing. Other complications of Herlitz JEB may include fusion of the fingers and toes, abnormalities of the fingernails and toenails, joint deformities (contractures) that restrict movement and hair loss (alopecia). Because the signs and symptoms of Herlitz JEB are so severe, infants with this condition usually do not survive beyond the first year of life.

Exuberant granulation tissue arising on the nape of the neck of a child with Herlitz JEB.

Fine Orphanet Journal of Rare Diseases 2010 5:12 

The milder form of JEB is called non-Herlitz JEB. The blistering associated with non-Herlitz JEB usually limited to the hands, feet, knees and elbows which often improves after the newborn period. Other characteristic features of non-Herlitz JEB include alopecia, malformed fingernails and toenails and irregular tooth enamel. Most affected individuals do not have extensive scarring or granulation tissue formation, so breathing difficulties and other severe complications are rare. Non-Herlitz JEB is typically associated with a normal lifespan.

A Rare kind of EBS

In rare cases of Epidermolysis Bullosa Simplex (EBS), no KRT5 or KRT14 gene mutations have been identified. Mutations in another gene — ‘PLEC’ — have been associated with the uncommon ‘Ogna type’ of the condition. The PLEC gene provides instructions for making a protein called ‘Plectin’ which helps the ‘Epidermis’ to attach with the underlying layers of skin.

Research is going in the search of PLEC gene mutations in people with EBS. Researchers are also working on how these mutations lead to the major features of Epidermolysis Bullosa Simplex [EBS].