Bchetnia Mbarka, Benmously Rym, Ben Brick Ahlem Sabrine, Charfeddine Cherine, Ben Ameur Youssef, Fajraoui Mohamed, Debbiche Achraf, Ben Ayed Mohamed, Mokni Mourad, Fenniche Samy, Mokhtar Inçaf, Abdelhak Sonia
Molecular Investigation of Genetic Orphan Diseases Research Unit, Institut Pasteur de Tunis, Pasteur, 1002 Tunis Belvédère, Tunisia.
Arch Dermatol Res. 2009 Sep;301(8):615-9. doi: 10.1007/s00403-009-0963-5. Epub 2009 Jun 2.
Darier's disease (DD, MIM 124200) also known as Darier-White disease and keratosis follicularis, is a rare autosomal dominant skin disorder characterized by warty papules and plaques in the seborrheic area (central trunk, flexures, scalp, and forehead). Pathogenic mutations in the ATP2A2 gene encoding the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA) 2 gene underlie the disease. In the present study, we performed genetic investigation of three unrelated Tunisian families affected by DD. Mutation screening was performed by direct sequencing of the coding region and exon/intron boundaries of the ATP2A2 gene. Patients in the 3 studied families exhibited classical DD phenotype. DD was associated with neurological and cardiac disorders in one family. Two novel mutations were identified: a missense mutation (R559Q) and a frameshift mutation (1713-1714 del 2A). Both pathogenic mutations are located in exon 13 of the ATP2A2 gene and affected the ATP-binding site of the SERCA2 protein. In one family, no mutation was found within the coding region and exon/intron boundaries of the ATP2A2 gene. Our findings provide further evidence for the genetic heterogeneity of DD in Tunisia and that most mutations involved in this disease are family specific.
达里埃病（DD，MIM 124200），也称为达里埃 - 怀特病和毛囊角化病，是一种罕见的常染色体显性遗传性皮肤病，其特征为在脂溢部位（躯干中部、屈侧、头皮和前额）出现疣状丘疹和斑块。编码肌浆网/内质网Ca(2+)ATP酶（SERCA）2的ATP2A2基因的致病突变是该疾病的基础。在本研究中，我们对三个不相关的受DD影响的突尼斯家庭进行了基因研究。通过对ATP2A2基因的编码区和外显子/内含子边界进行直接测序来进行突变筛查。所研究的3个家庭中的患者表现出典型的DD表型。在一个家庭中，DD与神经和心脏疾病有关。鉴定出两个新突变：一个错义突变（R559Q）和一个移码突变（1713 - 1714del 2A）。这两个致病突变均位于ATP2A2基因的第13外显子中，并影响了SERCA2蛋白的ATP结合位点。在一个家庭中，在ATP2A2基因的编码区和外显子/内含子边界内未发现突变。我们的研究结果为突尼斯DD的遗传异质性提供了进一步的证据，并且该疾病中涉及的大多数突变是家族特异性的。
