Seddon J M, Sharma S, Chong S, Hutchinson A, Allikmets R, Adelman R A
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA.
Ophthalmology. 2003 Sep;110(9):1724-31. doi: 10.1016/S0161-6420(03)00575-X.
To evaluate mutations in the Best mascular dystrophy (VMD2) gene in two families with Best disease and to describe the phenotype-genotype correlations of genetically determined affected and unaffected individuals.
Family genetic study.
Two families with Best disease were identified, and family members were evaluated by ophthalmologic examination or fundus photography to assess their phenotype. All affected patients and some of the unaffected family members had a blood sample drawn, and the DNA was analyzed for mutations in the VMD2 gene.
Twenty-one subjects in the two pedigrees with Best disease were studied. One amino acid-changing mutation in the VMD2 gene was found to segregate independently in each family (P297S or E300D, respectively).
Eleven individuals had some evidence of maculopathy, including retinal pigment epithelial changes, drusen, pigment epithelial irregularities, or cicatricial changes. Ten of these 11 patients (91%) with maculopathy had a mutation in the VMD2 gene, of whom 8 were clinically diagnosed as having Best disease and 2 were diagnosed as having possible Best maculopathy. The one patient without a mutation in the VMD2 gene had age-related macular degeneration (AMD). Ten family members did not have evidence of maculopathy, of whom 6 had no mutation in the VMD2 gene. Four family members (2 in each pedigree) had mutations in the VMD2 gene, abnormal electro-oculogram (EOG) results, but normal maculae at age 40 or older. Of the 7 individuals with no mutation in the VMD2 gene, 6 were phenotypically normal and the other had late-onset visual loss resulting from AMD.
All family members with maculopathy consistent with Best disease (n = 10) had an amino acid-changing mutation in the VMD2 gene. Four individuals who did not have maculopathy, but did have an abnormal EOG, also had mutations in the VMD2 gene. The presence of a VMD2 mutation is associated with abnormal retinal function, which can occur in the absence of phenotypic manifestation of macular disease.
评估两个患有贝斯特病的家系中贝斯特黄斑营养不良（VMD2）基因的突变情况，并描述经基因检测确定的患病和未患病个体的表型-基因型相关性。
家系遗传学研究。
确定了两个患有贝斯特病的家系，通过眼科检查或眼底摄影对家庭成员进行评估以确定其表型。所有患病患者和部分未患病家庭成员采集血样，分析VMD2基因的突变情况。
研究了两个患有贝斯特病家系中的21名受试者。发现VMD2基因中的一个氨基酸改变突变在每个家系中独立分离（分别为P297S或E300D）。
11名个体有黄斑病变的某些证据，包括视网膜色素上皮改变、玻璃膜疣、色素上皮不规则或瘢痕性改变。这11名患有黄斑病变的患者中有10名（91%）VMD2基因发生突变，其中8名临床诊断为贝斯特病，2名诊断为可能的贝斯特黄斑病变。1名VMD2基因未发生突变的患者患有年龄相关性黄斑变性（AMD）。10名家庭成员没有黄斑病变的证据，其中6名VMD2基因未发生突变。4名家庭成员（每个家系2名）VMD2基因发生突变，眼电图（EOG）结果异常，但40岁及以上时黄斑正常。在7名VMD2基因未发生突变的个体中，6名表型正常，另1名因AMD导致迟发性视力丧失。
所有符合贝斯特病的黄斑病变家庭成员（n = 10）VMD2基因均有氨基酸改变突变。4名没有黄斑病变但EOG异常的个体VMD2基因也发生了突变。VMD2突变的存在与视网膜功能异常有关，这在黄斑疾病无表型表现时也可能发生。
