Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or cone-rod degeneration.
Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or cone-rod degeneration.
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发表时间：
2001-09
影响因子：
4.4
通讯作者：
C. Briggs;David E. Rucinski;P. Rosenfeld;T. Hirose;E. Berson;T. Dryja
中科院分区：
文献类型：
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作者：
C. Briggs;David E. Rucinski;P. Rosenfeld;T. Hirose;E. Berson;T. Dryja
目的确定与Stargardt黄斑变性和视锥视杆细胞变性(CRD)相关的ABCR基因突变谱。方法采用单链构象多态性分析方法，对118例隐性Stargardt黄斑变性患者和8例隐性CRD患者进行ABCR(ABCA4)基因突变筛查。通过基因组直接测序对突变体进行鉴定。对20名患者的家庭进行分离分析，其中至少发现两种或更多可能的致病序列变化。结果作者发现77个可能致病的序列改变：21个零突变(15个新)，55个错义改变(26个新)，以及一个共同的糖基化位点的缺失(也是新的)。52名Stargardt黄斑变性患者(占筛查患者的44%)和5名CRD患者各有两个这样的序列变化或其中一个是纯合子。对其中19名患者的家庭进行的分离分析提供了信息，显示指示病例和所有可用的受影响兄弟姐妹都是复合杂合子或纯合子。作者在一名患者身上发现了一例明显的从头突变，Ile824Thr。在118例Stargardt病和1例CRD患者中，37例(31%)只有一个可能的致病序列改变。29名Stargardt病患者(25%)和2名CRD患者没有识别的序列变化。结论这份42个新突变的报告使ABCR中识别的可能致病序列变化的数量增加到约250个。
PURPOSE To determine the spectrum of ABCR mutations associated with Stargardt macular degeneration and cone-rod degeneration (CRD). METHODS One hundred eighteen unrelated patients with recessive Stargardt macular degeneration and eight with recessive CRD were screened for mutations in ABCR (ABCA4) by single-strand conformation polymorphism analysis. Variants were characterized by direct genomic sequencing. Segregation analysis was performed on the families of 20 patients in whom at least two or more likely pathogenic sequence changes were identified. RESULTS The authors found 77 sequence changes likely to be pathogenic: 21 null mutations (15 novel), 55 missense changes (26 novel), and one deletion of a consensus glycosylation site (also novel). Fifty-two patients with Stargardt macular degeneration (44% of those screened) and five with CRD each had two of these sequence changes or were homozygous for one of them. Segregation analyses in the families of 19 of these patients were informative and revealed that the index cases and all available affected siblings were compound heterozygotes or homozygotes. The authors found one instance of an apparently de novo mutation, Ile824Thr, in a patient. Thirty-seven (31%) of the 118 patients with Stargardt disease and one with CRD had only one likely pathogenic sequence change. Twenty-nine patients with Stargardt disease (25%) and two with CRD had no identified sequence changes. CONCLUSIONS This report of 42 novel mutations brings the growing number of identified likely pathogenic sequence changes in ABCR to approximately 250.