Jalkanen Reetta, Bech-Hansen N Torben, Tobias Rose, Sankila Eeva-Marja, Mäntyjärvi Maija, Forsius Henrik, de la Chapelle Albert, Alitalo Tiina
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Biomedicum Helsinki, Helsinki, Finland.
Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2498-502. doi: 10.1167/iovs.06-1103.
Aland Island eye disease (AIED), also known as Forsius-Eriksson syndrome, is an X-linked recessive retinal disease characterized by a combination of fundus hypopigmentation, decreased visual acuity, nystagmus, astigmatism, protan color vision defect, progressive myopia, and defective dark adaptation. Electroretinography reveals abnormalities in both photopic and scotopic functions. The gene locus for AIED has been mapped to the pericentromeric region of the X-chromosome, but the causative gene is unknown. The purpose of this study was to identify the mutated gene underlying the disease phenotype in the original AIED-affected family.
All exons of the CACNA1F gene were studied by DNA sequencing. CACNA1F mRNA from cultured lymphoblasts was analyzed by RT-PCR and cDNA sequencing.
A novel deletion covering exon 30 and portions of flanking introns of the CACNA1F gene was identified in patients with AIED. Results from expression studies were consistent with the DNA studies and showed that mRNA lacked exon 30. The identified in-frame deletion mutation is predicted to cause a deletion of a transmembrane segment and an extracellular loop within repeat domain IV, and consequently an altered membrane topology of the encoded alpha1-subunit of the Ca(v)1.4 calcium channel.
Mutations in CACNA1F are known to cause the incomplete form of X-linked congenital stationary night blindness (CSNB2). Since the clinical picture of AIED is quite similar to CSNB2, it has long been discussed whether these disorders are allelic or form a single entity. The present study clearly indicates that AIED is also caused by a novel CACNA1F gene mutation.
奥兰群岛眼病（AIED），也称为福西厄斯 - 埃里克森综合征，是一种X连锁隐性视网膜疾病，其特征为眼底色素减退、视力下降、眼球震颤、散光、红色盲、进行性近视和暗适应缺陷。视网膜电图显示明视觉和暗视觉功能均异常。AIED的基因座已定位到X染色体的着丝粒周围区域，但致病基因尚不清楚。本研究的目的是在最初受AIED影响的家系中鉴定导致疾病表型的突变基因。
通过DNA测序研究CACNA1F基因的所有外显子。通过RT-PCR和cDNA测序分析来自培养的淋巴母细胞的CACNA1F mRNA。
在AIED患者中鉴定出一个新的缺失，该缺失覆盖CACNA1F基因的第30外显子和部分侧翼内含子。表达研究结果与DNA研究一致，表明mRNA缺少第30外显子。鉴定出的框内缺失突变预计会导致跨膜片段和重复结构域IV内的细胞外环缺失，从而导致Ca(v)1.4钙通道编码的α1亚基的膜拓扑结构改变。
已知CACNA1F突变会导致X连锁先天性静止性夜盲（CSNB2）的不完全形式。由于AIED的临床表现与CSNB2非常相似，长期以来一直在讨论这些疾病是等位基因还是构成一个单一实体。本研究清楚地表明，AIED也是由一种新的CACNA1F基因突变引起的。
