Department of Ophthalmology and Visual Sciences, Carver Family Center for Macular Degeneration, University of Iowa, Iowa City, Iowa 52242, USA.
Retina. 2011 Mar;31(3):581-95. doi: 10.1097/IAE.0b013e318203ee60.
To report 11 cases of autosomal recessive vitelliform macular dystrophy and to compare their molecular findings and phenotypic characteristics with those of patients with the more common and well-described dominant form of the disease.
Blood samples were obtained from 435 unrelated individuals with a clinical diagnosis of vitelliform macular dystrophy and screened for mutations in the coding sequences of BEST1. Medical records and retinal photographs of selected patients were reviewed.
Nine of the 435 probands were found to have 2 plausible disease-causing variations in BEST1, while 198 individuals were found to have heterozygous variations compatible with autosomal dominant inheritance. Inheritance phase was determined in three of the recessive families. Six novel disease-causing mutations were identified among these recessive patients: Arg47Cys, IVS7-2A>G, IVS7+4G>A, Ile205del12ATCCTGCTCCAGAG, Pro274Arg, and Ile366delCAGGTGTGGC. Forty-four novel disease-causing mutations were identified among the patients with presumed autosomal dominant disease. The phenotype of patients with recessive alleles for BEST1 ranged from typical vitelliform lesions to extensive extramacular deposits.
The authors provide evidence that two abnormal BEST1 alleles, neither of which causes macular disease alone, can act in concert to cause early-onset vitelliform macular dystrophy.
报道 11 例常染色体隐性型类卵黄样黄斑营养不良，并将其分子发现和表型特征与更为常见和描述详尽的显性型疾病患者进行比较。
从 435 名经临床诊断为类卵黄样黄斑营养不良的无血缘关系个体中抽取血样，对 BEST1 的编码序列进行突变筛查。回顾性分析选定患者的病历和眼底照片。
在这 435 名先证者中，有 9 名被发现携带 2 种可能导致疾病的 BEST1 变异，而 198 名个体则携带与常染色体显性遗传一致的杂合变异。在 3 个隐性家族中确定了遗传阶段。在这些隐性患者中发现了 6 种新的致病突变：Arg47Cys、IVS7-2A>G、IVS7+4G>A、Ile205del12ATCCTGCTCCAGAG、Pro274Arg 和 Ile366delCAGGTGTGGC。在假定为常染色体显性疾病的患者中发现了 44 种新的致病突变。携带 BEST1 隐性等位基因的患者的表型范围从典型的类卵黄样病变到广泛的黄斑外沉积。
作者提供的证据表明，两种异常的 BEST1 等位基因，单独一种都不会引起黄斑病变，它们可以协同作用导致早发性类卵黄样黄斑营养不良。
