Castori Marco, Barboni Luana, Duncan Philippa J, Paradisi Mauro, Laino Luigi, De Bernardo Carmelilia, Robinson David O, Grammatico Paola
Experimental Medicine Department, 'Sapienza-University of Rome', San Camillo-Forlanini Hospital, Italy.
Am J Med Genet A. 2009 Aug;149A(8):1768-72. doi: 10.1002/ajmg.a.32960.
Darier disease (DD) is an autosomal dominant genodermatosis caused by mutations in ATP2A2 and characterized by multiple warty papules coalescing in seborrheic areas and specific histological skin changes. Rare patients are described with variable bone involvement, but this association has never been sufficiently emphasized. Aniridia is a developmental disorder of the eye due to heterozygous mutations in PAX6. DD and aniridia are Mendelian traits mapping on independent loci and have never been reported in association. Here, we describe a 14-year-old girl showing the unique combination of DD, multiple bone cysts, and bilateral aniridia. Molecular investigations demonstrated that such a complex phenotype is due to double de novo heterozygous mutations in ATP2A2 and PAX6. Review of the literature indicates that, in DD, bone cysts are true developmental abnormalities of the skeleton. This finding suggests a role for ATP2A2 in bone biology. More systematic studies are expected in order to estimate the true prevalence of bone cysts in DD and the relationship between skeletal changes and ATP2A2 perturbation.
Darier病（DD）是一种常染色体显性遗传性皮肤病，由ATP2A2基因突变引起，其特征为在脂溢性区域有多个疣状丘疹融合以及特定的皮肤组织学改变。有少数患者被描述有不同程度的骨骼受累情况，但这种关联从未得到充分强调。无虹膜症是一种由于PAX6基因杂合突变导致的眼部发育障碍。DD和无虹膜症是位于独立基因座上的孟德尔性状，此前从未有过相关报道。在此，我们描述了一名14岁女孩，她表现出DD、多发性骨囊肿和双侧无虹膜症的独特组合。分子研究表明，这种复杂的表型是由于ATP2A2和PAX6基因的双新发杂合突变所致。文献回顾表明，在DD中，骨囊肿是骨骼真正的发育异常。这一发现提示ATP2A2在骨骼生物学中发挥作用。预计将进行更系统的研究，以估计DD中骨囊肿的真实患病率以及骨骼变化与ATP2A2功能紊乱之间的关系。
