Ichthyosis vulgaris ichthyosis-single (Ichthyosis vulgaris-Ichthyosis Simplex) - Gen FLG.

Ichthyosis encompasses a group of skin diseases which are characterized by cornification (excessive accumulation of large amounts of flakes or dead cells) in the top layer of skin. Ichthyosis vulgaris is characterized by a slight hyperkeratosis and an absence or decrease in the epidermis of the keratohyalin granules and profilaggrin, proteins with a role in normal cornification.

Many individuals with ichthyosis have darkened and rough skin, with large scales separated by deep cracks. Others have an extremely fragile, bullous skin, which may peel off easily. This dry and rigid skin makes any movement uncomfortable as it can cause the skin to crack and break. Even the excessive thickening of the soles of the feet, makes it difficult to walk, like the cracking of the skin of the fingers, can lead to the simplest tasks become difficult and painful. In general, these signs and symptoms are more evident in the lower abdomen, arms and legs. In addition, they may have other effects such as tightness in the eyelids, lips, problems with hair growth and psychomotor problems. Other symptoms may include frequently asthma. The severity of ichthyosis ranges from mild dryness, though annoying, intense dryness with scaling that can be disfiguring.

This disease is due to mutations in the FLG gene, located on the long arm of chromosome 1 (1q21.3). This gene encodes an intermediate filament associated protein that aggregates keratin intermediate filaments in the epidermis. It is initially synthesized as a polyprotein precursor, profilaggrin (consisting of several units of filaggrin 324 amino acids each), located in the keratohyalin granules, and subsequently proteolytically processed into filaggrin individual functional molecules.

Several mutations have been identified in the FLG gene in people with ichthyosis vulgaris. Mutations in the gene cause a loss of filaggrin protein. A homozygous mutation, R501X, near the start of repeat 1 in exon 3 of the FLG gene and a second mutation, 2282del4 in exon 3 of the FLG gene, protein translation stop within the first filaggrin repeat. Other mutations are identified S2554X and 3321delA.

The most common form of ichthyosis is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to result in the alteration.

Tests in IVAMI: in IVAMI perform detection of mutations associated with ichthyosis vulgaris, by complete PCR amplification of exons FLG gene, 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).