Monilethrix – DSG4, KRT81, KRT83 and KRT86 genes 

            Monilethrix is ​​an alteration that affects hair growth. Its most characteristic feature is that individual strands of hair have a twisted appearance, like the beads of a necklace, due to the periodic narrowing of the hair shaft. The alteration is evident when viewed under a microscope. Affected people also have poor and short hair growth, which is fragile that breaks easily.

Usually, affected people have normal hair at birth, developing hair abnormalities in the first months of life. In mild cases of the alteration, only the hair on the back of the head or neck is affected. In more severe cases, hair on the entire scalp can be affected, as well as pubic hair, underarm hair, eyebrows, eyelashes and hair on the arms and legs. Occasionally, the skin and nails are also affected. Some people have keratosis pilaris, which has small bumps on the skin, especially in the scalp, neck and arms. Affected individuals may also have abnormal nails.

This process is due to mutations in the genes DSG4, KRT81, KRT83 and KRT86, which encode proteins that give structure and stiffness to the hair.

The DSG4 gene, located on the long arm of chromosome 18 (18q12.1), encodes desmoglein 4 (DSG4) protein. This protein is found in specialized structures called desmosomes that are found in the membrane that surrounds certain cells. These structures help fix the cells to each other and play a role in signaling between the cells. Desmoglein 4 (DSG4) protein is found in certain regions of the hair follicle, including the hair cuticle. Mutations associated with this disease can affect any part of the protein, but these changes generally alter the extracellular domain. It is not clear how mutations in the DSG4 gene are related to cuticle abnormality or hair alteration.

The genes KRT81 (12q13), KRT83 (12q13) and KRT86 (12q13), encode keratin proteins. Keratins are a group of rigid and fibrous proteins that form the structural framework of the cells that form hair, skin and nails. The KRT81 gene encodes keratin hair protein type II K81 (K81); The KRT83 gene encodes the keratin hair protein type K83 (K83) and the KRT86 gene encodes the keratin hair protein type II K86 (K86). These proteins are found in the cells of the inner compartment of the hair shaft known as the cuticle. These proteins give the hair its stiffness and elasticity. Mutations in these genes change a single amino acid in the protein. Amino acid changes usually occur in a region of the protein that is thought to be important in the formation of intermediate filaments. It is not clear how mutations in the KRT81, KRT83, KRT86 genes are related to the abnormality of the cortex or the alteration of the hair.

The disease can have multiple inheritance patterns. When the condition is caused by a mutation in one of the keratin genes, it is inherited with an autosomal dominant pattern, which means that a copy of the altered gene in each cell is sufficient to cause the alteration. In rare cases, are due to a new mutation in the gene that has not been inherited. When the condition is caused by mutations in the DSG4 gene, it is inherited with an autosomal recessive pattern, which means that both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease. 

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with Monilethrix, by means of the complete PCR amplification of the exons of the DSG4, KRT81, KRT83 y KRT86 genes, respectively, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).