How PLOD1 Gene Cause EDS?

More than 20 mutations have been identified in the PLOD1 gene which causes Kyphoscoliosis Types of EDS. The most common mutation duplicates a large portion of the gene, resulting in the production of a non-functional version of the ‘lysyl hydroxylase 1’ enzyme. Several other mutations introduce premature stop signals that prevent the gene from making any functional enzyme. A loss of lysyl hydroxylase 1 activity impairs cross-linking between collagen molecules. This disruption in the network of collagen fibrils weakens connective tissues, causing the signs and symptoms of Ehlers-Danlos syndrome.

Source: www.ghr.nlm.nih.gov

PLOD1 Gene … Normal Function

The PLOD1 gene provides instructions for making an enzyme called ‘lysyl hydroxylase 1’ — which modifies a particular amino acid called ‘lysine’, one of the building blocks used to make proteins. Specifically, ‘lysyl hydroxylase 1’ adds a single oxygen atom to a hydrogen atom to create a charged molecule called a ‘hydroxyl group’. Hydroxyl groups attach to some of the ‘lysines’ in collagen-like proteins. We already know that ‘Collagens’ are complex molecules which provide strength, support and elasticity (the ability to stretch) to many body tissues.

‘Hydroxyl groups’ are essential for collagen molecules to form stable interactions — called cross-links — with one another. Cross-links between these molecules allow collagen to form networks of strong, slender fibrils, which are an important part of the normal structure of connective tissue which binds and supports the body's muscles, ligaments, organs, and skin.

Source: www.ghr.nlm.nih.gov

PLOD1 Gene … Location

Cytogenetic Location      :      1p36.22

Molecular Location         :      Chromosome 1

Base pairs (Bp) 11,994,723 - 12,035,598

The PLOD1 gene is located on the long (q) arm of ‘chromosome 1’ at position 36.22, more precisely, from BP 11,994,723 ~ 12,035,598 on chromosome 1.

Source: www.ghr.nlm.nih.gov

PLOD1 Gene ... Official name

PLOD1 gene is responsible for 'Kyphoscoliosis Types'.

Official Name     :      procollagen-lysine,2-oxoglutarate 5-dioxygenase 1

Official Symbol      :      PLOD1

Other names of COL5A2 Gene

@ Collagen Lysyl Hydroxylase

@ LH

@ LH1

@ LLH

@ Lysine 2-Oxoglutarate Dioxygenase

@ Lysine Hydroxylase

@ Lysyl Hydroxylase

@ PLOD

@ PLOD1_HUMAN

@ Procollagen-L-lysine,2-oxoglutarate:oxygen oxidoreductase (5-hydroxylating)

@ procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1

@ procollagen-lysine, 2-oxoglutarate 5-dioxygenase (lysine hydroxylase, Ehlers-Danlos syndrome type VI)

@ Protocollagen Lysyl Hydroxylase

Source: www.ghr.nlm.nih.gov

How COL3A1 Gene Cause EDS?

More than 320 mutations in the COL3A1 gene cause the ‘Vascular Type’ of Ehlers-Danlos Syndrome (EDS). Only a few of these mutations have been seen in more than one family. The mutations alter the structure and production of type III procollagen molecules. As a result, a large percentage of type III collagen molecules are assembled incorrectly or the amount of type III collagen is greatly reduced.

As per research, these changes affect tissues which are normally rich in this type of collagen such as the skin, blood vessels, and internal organs. Lack of sufficient type III collagen causes the signs and symptoms of ‘Vascular Ehlers-Danlos Syndrome’.

COL3A1 Gene … Normal Function

Type III collagen is found in tissues such as the skin, lungs, intestinal walls, and the walls of blood vessels. The COL3A1 gene produces the components of type III collagen, called pro-alpha1 (III) chains. 3 copies of this chain combine to make a molecule of type III procollagen. These triple-stranded, rope-like procollagen molecules must be processed by enzymes outside the cell to remove extra protein segments from their ends. Once these molecules are processed, the collagen molecules arrange themselves into long, thin fibrils. Within these fibrils, the individual collagen molecules are cross-linked to one another. These cross-links result in the formation of very strong mature type III collagen fibrils, which are found in the spaces around cells.

COL3A1 Gene … Location

Cytogenetic Location      :      2q31

Molecular Location         :      Chromosome 2

Base pairs (Bp) 189,839,098 - 189,877,471

The COL3A1 gene is located on the long (q) arm of ‘chromosome 2’ at position 31, more precisely, from BP 189,839,098 ~ 189,877,471 on chromosome 2.

Source: www.ghr.nlm.nih.gov

COL3A1 Gene ... Official Name

COL3A1 gene is responsible for 'Vascular Types', most severe form of Ehlers-Danlos syndrome (EDS)

Official Name        :      Collagen, type III, alpha 1

Official Symbol      :      COL3A1

Other names of COL5A2 Gene

@ alpha 1 type III collagen

@ CO3A1_HUMAN

@ collagen, fetal

@ Collagen III, alpha-1 polypeptide

@ Collagen, type III, alpha 1 (Ehlers-Danlos syndrome type IV, autosomal dominant)

@ EDS4A

Source: www.ghr.nlm.nih.gov

How COL5A2 Gene Cause EDS?

Mutations in the COL5A2 gene have been identified in a small number of patients with classic Ehlers-Danlos syndrome (EDS). These mutations change the structure and function of the pro-alpha2 (V) chain. As a result, type V collagen fibrils in the skin which are assembled with the altered protein are large and irregular.

Research is going on how these changes in collagen structure cause the signs and symptoms of classical Ehlers-Danlos syndrome (EDS).

COL5A2 Gene … Normal Function

We already discussed about the ‘Collagen Protein’ in our COL5A1 gene discussion. 

The COL5A2 gene produces a component of type V collagen, called the pro-alpha2 (V) chain. 1 pro-alpha2 (V) chain combines with 2 pro-alpha1 (V) chains (produced by the COL5A1 gene) to form ‘Type V pro-collagen’.

These triple-stranded, rope-like pro-collagen molecules must be processed by enzymes outside the cell. Once these molecules are processed, they arrange themselves into long, thin fibrils that cross-link to one another in the spaces around cells. The cross-links result in the formation of very strong, mature type V collagen fibers.

As we discussed earlier ‘Type V collagen’ also plays a role in assembling other types of collagen into fibrils within many connective tissues.

Source: www.ghr.nlm.nih.gov

COL5A2 Gene … Location

Cytogenetic Location      :      2q14-q32

Molecular Location         :      Chromosome 2

Base pairs (Bp) 189,896,640 - 190,044,604

The COL5A2 gene is located on the long (q) arm of ‘chromosome 2’ between positions 14 and 32, more precisely, from BP 189,896,640 ~ Bp 190,044,604 on chromosome 2.

Source: www.ghr.nlm.nih.gov

COL5A2 Gene ... Official Name

The 2^nd gene responsible for 'Classic Types' of Ehlers-Danlos syndrome (EDS) is COL5A2.

Official Name        :      Collagen, type V, alpha 2

Official Symbol      :      COL5A2

Other names of COL5A2 Gene

@ AB collagen

@ CO5A2_HUMAN

@ Collagen, fetal membrane, A polypeptide

@ Collagen V, alpha-2 polypeptide

Source: www.ghr.nlm.nih.gov

How COL5A1 Gene cause EDS …

More than 50% of cases of classical Ehlers-Danlos syndrome (EDS) are caused by mutations in the COL5A1 gene. Many of these mutations lead to a non-functional/absent pro-alpha1 (V) chain. As a result, type V collagen fibrils in the skin and other tissues cannot be assembled correctly. The fibrils are disorganized and larger than usual.

Research is going on how these changes in collagen structure cause the signs and symptoms of classical Ehlers-Danlos syndrome (EDS).

COL5A1 gene ... Normal Function

Collagens form a family of proteins which strengthen & support many tissues in the body such as skin, ligaments, bones, tendons, muscles and the extracellular matrix between cells & tissues.

The COL5A1 gene produces a component of type V collagen — pro-alpha1 (V) chain. 3 of these chains combine to make a molecule of type V pro-collagen. Alternatively, 2 of these chains can also combine with 1 pro-alpha2 (V) chain (produced by the COL5A2 gene) to form type V pro-collagen.

These triple-stranded rope-like pro-collagen molecules must be processed by enzymes outside the cell. Once these molecules are processed, they arrange themselves into long, thin fibrils that cross-link to one another in the spaces around cells. The cross-links result in the formation of very strong, mature type V collagen fibers.

Type V collagen also plays a role in assembling other types of collagen into fibrils within many connective tissues and also essential for the formation of normal type I collagen fibrils.

Source: www.ghr.nlm.nih.gov

COL5A1 Gene ... Location

Cytogenetic Location     :      9q34.2-q34.3

Molecular Location        :      Chromosome 9 :

Base pairs (Bp) 137,533,651 - 137,736,688

The COL5A1 gene is located on the long (q) arm of ‘chromosome 9’ between positions 34.2 and 34.3, more precisely, from BP 137,533,651 ~ Bp 137,736,688 on chromosome 9.

Source: www.ghr.nlm.nih.gov