Compound Heterozygous Mutations Including a De Novo Missense Mutation in ABCA12 Led to a Case of Harlequin Ichthyosis with Moderate Clinical Severity

Masashi Akiyama, Kaori Sakai, Yoriko Sugiyama-Nakagiri, Yasuko Yamanaka, James R. McMillan, Daisuke Sawamura, Hironori Niizeki, Sachiko Miyagawa, Hiroshi Shimizu
2006 Journal of Investigative Dermatology  
Harlequin ichthyosis (HI) is one of the most devastating genodermatoses. Recently, ABCA12 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 1160G4A (S387N) in exon 10 and a maternal deletion mutation 4158_4160delTAC
more » ... el) in exon 28 of ABCA12. T1387del was a deletion of a highly conserved threonine residue within the first adenosine 5 0 triphosphatebinding domain and is thought to seriously affect the function of the ABCA12 protein. Conversely, the residue 387 is located outside the known active sites of ABCA12 and S387N is predicted not to lead to a serious functional deficiency in ABCA12. 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 ABCA12 has yet been reported either in HI or lamellar ichthyosis. The present case suggested that a de novo ABCA12 mutation might underlie HI.
doi:10.1038/sj.jid.5700295 pmid:16675967 fatcat:j5kbh7i2b5gwhhsvvh56dhhjym