Compound heterozygous mutations including a de novo missense mutation in ABCA12 led to a case of harlequin ichthyosis with moderate clinical severity
Compound heterozygous mutations including a de novo missense mutation in ABCA12 led to a case of harlequin ichthyosis with moderate clinical severity
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DOI：
10.1038/sj.jid.5700295
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发表时间：
2006-07-01
影响因子：
6.5
通讯作者：
Shimizu, Hiroshi
中科院分区：
文献类型：
--
作者：
Akiyama, Masashi;Sakai, Kaori;Shimizu, Hiroshi
丑角鱼鳞病（HI）是最具破坏性的遗传性皮肤病之一。最近，ABCA12突变被确定为HI的原因。一例日本男性新生儿表现出HI的典型特征。患者接受口服依曲替酸治疗，一般状况良好（现在年龄为1.5岁）。该中度临床严重程度的患者是ABCA 12外显子10中的新型从头错义突变1160G > A（S387N）和外显子28中的母体缺失突变4158_4160delTAC（T1387del）的复合杂合型。T1387del是第一个腺苷50三磷酸结合结构域内高度保守的苏氨酸残基的缺失，并且被认为严重影响ABCA 12蛋白的功能。相反，残基387位于ABCA 12的已知活性位点之外，并且预测S387N不会导致ABCA 12中的严重功能缺陷。电镜下可见颗粒层细胞内有异常片状颗粒，皮质细胞内有中等数量的脂质空泡。在患者培养的角质形成细胞中证实了葡萄糖神经酰胺转运紊乱。在HI或板层状鱼鳞病中，ABCA 12的新发突变尚未报道。目前的情况表明，从头ABCA 12突变可能是HI的基础。
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 1160G > A (S387N) in exon 10 and a maternal deletion mutation 4158_4160delTAC (T1387del) in exon 28 of ABCA12. T1387del was a deletion of a highly conserved threonine residue within the first adenosine 50 triphosphate-binding 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.