Mutation and expression of ABCA12 in keratosis pilaris and nevus comedonicus

Abstract

Keratosis pilaris (KP) and nevus comedonicus (NC) are congenital keratinized dermatoses; however, the exact etiology of these two diseases is unclear. The objective of the present study was to identify the disease-causing genes and their association with functional alterations in the development of KP and NC. Peripheral blood samples of one KP family, two NC families and 100 unrelated healthy controls were collected. The genomic sequences of 147 genes associated with 143 genetic skin diseases were initially analyzed from the KP proband using a custom-designed GeneChip. A novel heterozygous missense mutation in the ATP-binding cassette sub-family A member 12 (ABCA12) gene, designated c.6694G>T (p.Asp2232Tyr), was identified in the KP proband and confirmed by Sanger sequencing. The same mutation was also present in the affected family members but not in the healthy family members, the two patients with NC or population-matched controls. The predictions provided by PolyPhen-2 and SIFT analyses suggested that the mutation may produce a damaged protein. The region surrounding the mutation is the extra-membrane domain, which is conserved among particular species, as suggested by ClustalX; however, no ABCA12 mutations were reported in the patients with NC. As observed by immunofluorescence, ABCA12 expression was upregulated in the sebaceous glands of the patients with NC compared with that of normal controls. In summary, ABCA12-associated mutations or alterations in expression may exhibit causative or contributive effects to the development of keratinized dermatoses, including KP and NC.

Clinical and genetic investigation of ichthyosis in familial and sporadic cases in south of Tunisia: genotype–phenotype correlation

“…This particular form of ichthyosis was explained by the combination of a germline mutation and an acquired postzygotic mutation in this gene. ABCA12 gene was reported also in a keratosis pilaris with missense mutation and in Nevus comedonicus with a high protein expression level in the sebaceous gland without any variation in ABCA12 coding region [ 40 ].…”

A Narrative Review on the Role of Acids, Steroids, and Kinase Inhibitors in the Treatment of Keratosis Pilaris

“…One study concluded that fibrinogen alpha chain genes impact keratosis pilaris because it codes for amino acids that produce the profilaggrin protein, which contributes to keratin and acid levels of the skin [13,33].…”

“…As previously stated, keratosis pilaris is a genetic condition; therefore, some of the genes producing amino acids can have some impact on keratosis pilaris. For example, fibrinogen alpha chain and guanine nucleotide exchange factor 1 genes code for amino acids that create proteins that have an effect on acne and hyperpigmentation [13,14]. However, this review generally focuses on steroids, kinase inhibitors, and types of acids that the majority of keratosis pilaris and other acne treatments consist of.…”

Zosteriform Nevus Comedonicus

“…The prevalence has been found to be between 1 in 45,000 to 1 in 100,000. Genetic mosaicism plays a role in the etiology of nevus comedonicus (Liu et al, 2018;Levinsohn et al, 2016). Individual lesions are multiple aggregated papules with open comedo like lesions topped with black colored keratin plugs.…”