Monilethrix (Monilethrix) - Genes DSG4, KRT81, KRT83 and KRT86.  

Monilethrix is a disorder that affects hair growth. Its most distinctive feature is that the individual strands of hair have a arrosariada appearance, like beads on a necklace, due to periodic narrowing of the hair shaft. Alteration is evident when viewed under a microscope. Affected individuals also have a limited and short hair growth, which is fragile is easily broken.

Usually, people affected have normal hair at birth, growing hair anomalies in the first months of life. In mild cases of the disturbance, only the hair on the back of the head or nape of the neck is affected. In more severe cases, it can be affected hair all over the scalp and pubic hair, underarm hair, eyebrows, eyelashes and hair on the arms and legs. Sometimes, skin and nails are also affected. Some people have keratosis pilaris, which causes small bumps on the skin, especially on the scalp, neck and arms. Affected individuals may also have abnormal fingernails.

This process is due to mutations in the DSG4, KRT81, KRT83 and KRT86 genes encoding proteins that provide structure and rigidity to the hair.

The DSG4 gene, located on the long arm of chromosome 18 (18q12.1), encoding the protein desmoglein 4 (DSG4). This protein is denominated in desmosome specialized structures found in the membrane surrounding certain cells. These structures help fix the cells together and play a role in signaling between cells. Desmoglein protein 4 (DSG4) is in some regions of the hair follicle, including the hair cuticle. Mutations associated with this disease can affect any part of the protein, but usually these changes alter the extracellular domain. It is unclear how mutations in the gene DSG4 are related to the abnormality in the cuticle hair or alteration.

The KRT81 (12q13), KRT83 (12q13) and KRT86 (12q13), genes encode proteins of keratins. Keratins are a group of rigid and fibrous proteins that form the structural framework of cells that make up hair, skin and nails. The gene encodes KRT81 keratin protein hair type II K81 (K81) keratin; gene encodes the KRT83 keratin protein hair type II K83 (K83) and the gene encodes KRT86 keratin protein hair type II K86 (K86). These proteins are found in the cells of the inner compartment of the hair shaft called the cuticle. These proteins give hair its strength and elasticity. Mutations in these genes change a single amino acid in the protein. The amino acid changes generally occur in a region of the protein that is thought to be important in forming intermediate filaments. It is unclear how mutations in KRT81, KRT83, KRT86 genes are related to abnormalities in the cortex or alteration of hair.

The disease can have multiple inheritance patterns. When the condition is caused by a mutation in one of keratin genes is inherited in 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, cases are due to a new mutation in the gene has not been inherited. When the condition is caused by mutations in the DSG4 gene is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with monilethrix, by complete PCR amplification of the exons of DSG4, KRT81, KRT83 and KRT86, respectively genes and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).