Mutation and expression of ABCA12 in keratosis pilaris and nevus comedonicus

摘要

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.6694GT (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.