Biological Significance of Ichthyosis

In Harlequin Ichthyosis (HI) affected epidermis, several morphologic abnormalities including abnormal lamellar granules in the keratinocyte granular layer and a lack of extracellular lipid lamellae within the stratum corneum had been reported. Lack of ABCA12 function subsequently leads to disruption of lamellar granule lipid transport in the upper keratinizing epidermal cells resulting in malformation of the intercellular lipid layers of the stratum corneum in HI. Cultured epidermal keratinocytes from an HI patient carrying ABCA12 mutations demonstrated defective glucosylceramide transport, and this phenotype was recoverable by in vitro ABCA12 corrective gene transfer. To date, intracytoplasmic glucosylceramide transport has been studied using cultured keratinocytes from a total of three patients harboring ABCA12 mutations. One patient was a homozygote for a splice site mutation c.3295_2A4G and another patient was a compound heterozygote for p.Ser387Asn and p.Thr1387del. Only one heterozygous mutation p.Ile1494Thr was identified in the other patient. Cultured keratinocytes from all the three patients showed apparently disturbed glucosylceramide transport, although this assay is not quantitative.