Gamundi María José, Hernan Imma, Maseras Miquel, Baiget Montserrat, Ayuso Carmen, Borrego Salud, Antiñolo Guillermo, Millán José María, Valverde Diana, Carballo Miguel
Laboratori de Biologia i Genetica Molecular, Hospital de Terrassa, Ctra. Torrebonica, Terrassa, Spain.
Mol Vis. 2005 Nov 2;11:922-8.
Only one mutation in the retinal fascin gene (FSCN2) has so far been associated with autosomal dominant retinitis pigmentosa (adRP) and macular dystrophy (adMD), in a Japanese population. Our study was designed to identify mutations in the FSCN2 gene among Spanish persons with adRP or adMD.
Denaturing gradient gel electrophoresis and direct genomic sequencing were used to evaluate the complete coding region and flanking intronic sequences of the FSCN2 gene for mutations in 150 unrelated adRP and 15 adMD index patients, and in 50 sporadic cases of retinitis pigmentosa, together with 50 controls. Ophthalmic and electrophysiological examination of retinitis pigmentosa patients and their relatives was carried out according to pre-existing protocols.
Sixteen nucleotide substitutions were detected in the coding sequence of the index patients. Nine of these, His7Tyr, Ala122Thr, Ser126Phe, His138Tyr, Arg149Gln, Ala240Thr, Ala323Thr, Asn331His, and Phe367Leu are missense mutations, one is a nonsense mutation (Lys302Stop), and six are silent mutations. Co-segregation of the mutations in the families showed no direct relation between mutation and disease.
The photoreceptor-specific FSCN2 gene showed a relatively high number of sequence variations. The mutation 208delG in FSCN2, the only mutation so far associated with adRP or adMD, and which presumably causes a null allele, was not detected in these Spanish families. The nonsense mutation, Lys302Stop, detected in one adRP Spanish family is not the cause of the disease. These findings support the fact that the kind and frequency of the mutations depend on the ethnic population.
迄今为止，在日本人群中，视网膜肌动蛋白结合蛋白基因（FSCN2）仅有一个突变与常染色体显性遗传性视网膜色素变性（adRP）和黄斑营养不良（adMD）相关。我们的研究旨在鉴定西班牙患有adRP或adMD的人群中FSCN2基因的突变情况。
采用变性梯度凝胶电泳和直接基因组测序，评估150例无亲缘关系的adRP患者、15例adMD先证者、50例散发性视网膜色素变性患者以及50例对照者的FSCN2基因完整编码区和侧翼内含子序列中的突变情况。根据现有方案，对视网膜色素变性患者及其亲属进行眼科和电生理检查。
在先证者的编码序列中检测到16个核苷酸替换。其中9个，即His7Tyr、Ala122Thr、Ser126Phe、His138Tyr、Arg149Gln、Ala240Thr、Ala323Thr、Asn331His和Phe367Leu为错义突变，1个为无义突变（Lys302Stop），6个为沉默突变。家族中突变的共分离显示突变与疾病之间无直接关联。
光感受器特异性FSCN2基因显示出相对较高数量的序列变异。在这些西班牙家族中未检测到FSCN2基因中208delG突变，该突变是迄今为止唯一与adRP或adMD相关的突变，并可能导致无效等位基因。在一个西班牙adRP家族中检测到的无义突变Lys302Stop并非该疾病的病因。这些发现支持了突变类型和频率取决于种族人群这一事实。
