FLG Gene, Mutation Analysis
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Ichthyosis vulgaris is a common disease with an incidence rate of approximately 1 in 250. It is characterized by palmar hyperlinearity, keratosis pilaris, xerosis, and prominent fine scaling of the extensor surfaces of the extremities, the scalp, central part of the face, and the trunk. The clinical onset typically occurs within the first few years of life. Approximately 37% to 50% of people with ichthyosis vulgaris have atopic diseases and about 8% of patients with atopic diseases have classic features of ichthyosis vulgaris. A large number of epidemiological studies support an increased risk and severity of asthma that occurs in association with atopic disease. Clinical presentation associated with ichthyosis vulgaris can be confirmed by genetic testing.
Ichthyosis vulgaris is caused by loss-of-function alterations in the filaggrin (FLG) gene on chromosome 1q21. Filaggrin is a filament aggregating protein that promotes terminal differentiation of the epidermis and skin barrier formation. This prevents epidermal water loss and inhibits entry of allergens, toxic chemicals, and infectious organisms. Loss of filaggrin expression causes cytoskeletal disorganization leading to clinical phenotype associated with ichthyosis vulgaris. FLG mutations are found in about 7.7% of Europeans and 3% of Asians. However, these mutations appear to be less common in dark-skinned ethnicities. The R501X and 2282del4 are complete loss-of-function mutations accounting for approximately 80% of mutations in the Northern European population. However, they are rarer in the Southern European population. These 2 alterations have been shown to be very strong predisposing factors for atopic diseases. FLG mutations in other ethnicities are different than those found in European-origin populations.
This disease is inherited in a semidominant manner (ie, heterozygotes have either no symptoms or milder ichthyosis vulgaris and homozygotes/compound heterozygotes show marked ichthyosis vulgaris).
Genetic diagnosis of ichthyosis vulgaris for clinical management, risk assessment for atopic diseases and atopic disease-associated asthma, and genetic counseling for family members
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This assay does not detect all of the mutations in filaggrin (FLG) gene or any other gene mutations that cause ichthyosis vulgaris. Therefore, the absence of a detectable mutation does not rule out the possibility that an individual is a carrier of, or affected with, ichthyosis vulgaris. For carrier testing, it is important to first document the presence of an FLG gene mutation in an affected family member.
Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.
Rare polymorphisms exist that could lead to false-negative or positive results. If results obtained do not match the clinical findings, additional testing should be considered.
Bone marrow transplants from allogenic donors will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Smith FJD, Irvine AD, Terron-Kwiatkowski A, et al: Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet 2006;38:337-342
2. Thyssen JP, Godoy-Gijon E, Elias PM: Ichthyosis vulgaris-the filaggrin mutation disease. Br J Dermatol 2013 Jun;168(6):1155-1166
3. Palmer CN, Irvine AD, Terron-Kwiatkowski A, et al: Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006 Apr;38(4):441-446