The ALOX12B gene encodes 12R-LOX, an enzyme belonging to the arachidonate lipoxygenase family. Enzymes in this family are responsible for catalyzing the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids into fatty acid hydroperoxides, which can then be transformed into signaling molecules. 12R-LOX specifically catalyzes the conversion of arachidonic acid to 12R-hydroperoxyeicosatetraenoic acid (12R-HPETE). By carrying out its function, the enzyme is believed to play a key role in the ceramide biosynthetic process and the establishment of the skin barrier to water loss.
Mutations in the ALOX12B gene that affect its enzyme activity can thus impair the formation of the lipid barrier in the skin’s epidermis. This results in Ichthyosis, Congenital, Autosomal Recessive 2 (ARCI2), an inflammatory form of ichthyosis characterized by prominent erythroderma, fine white, superficial, and semi-adherent scales, ectropion and eclabion
The gene is located on the short arm of chromosome 17. It spans a length of 15 kb of DNA and its coding sequence is spread across 15 exons. The protein product encoded by this gene has a molecular mass of 80.3 kDa and consists of 701 amino acids. The gene is expressed in B-cells, hair follicles, foreskin keratinocytes and adult skin. More than 30 mutations in ALOX12B have been found to cause ARCI2. A majority of these are missense mutations that result in a non-functional protein.
Bastaki et al. (2017) conducted a study to identify the underlying gene mutations in Emirati congenital ichthyosis patients. A female patient, born as a collodion baby with MRSA sepsis and bilateral pneumonia, was described. She exhibited generalized thick dry skin with ichthyosis on the soles, but by the age of 10 months, her skin condition greatly improved. She also had abnormal palmar creases, camptodactyly of the fifth fingers, Mongolian spot on the buttocks, cutis marmorata and dysmorphic features such as a broad forehead, a depressed broad nasal bridge, micrognathia, and malformed ears with thick helices. She was diagnosed with nonbullous CIE and WES uncovered a homozygous c.944T>C (p.Leu315Pro) mutation in exon 8 of the ALOX12B gene. The mutation was predicted to be functionally damaging and the patient’s consanguineous parents were both found to be heterozygous carriers.
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