Compound heterozygous mutations including a de novo missense mutation in ABCA12 led to a case of harlequin ichthyosis with moderate clinical severity.

[harlequin ichthyosis]

Harlequin ichthyosis (HI ) is one of the most devastating genodermatoses . Recently , ABCA 12 mutations were identified as the cause of HI . A newborn Japanese male demonstrated the typical features of HI . The patient was treated with oral etretinate and his general condition has been good (now aged 1 .5 years ). This patient with moderate clinical severity was compound heterozygous for a novel de novo missense mutation 1160 G > A (S 387 N ) in exon 10 and a maternal deletion mutation 4158 _4160 delTAC (T 1387 del ) in exon 28 of ABCA 12 . T 1387 del was a deletion of a highly conserved threonine residue within the first adenosine 5 ' triphosphate-binding domain and is thought to seriously affect the function of the ABCA 12 protein . Conversely , the residue 387 is located outside the known active sites of ABCA 12 and S 387 N is predicted not to lead to a serious functional deficiency in ABCA 12 . Electron microscopy revealed abnormal lamellar granules in the granular layer cells and a moderate number of lipid vacuoles in the cornified cells . Disturbed glucosylceramide transport was confirmed in the cultured keratinocytes from the patient . No de novo mutation in ABCA 12 has yet been reported either in HI or lamellar ichthyosis . The present case suggested that a de novo ABCA 12 mutation might underlie HI .