Mutations in the CRB1 gene cause Leber congenital amaurosis
Mutations in the CRB1 gene cause Leber congenital amaurosis
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DOI：
10.1001/archopht.119.3.415
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发表时间：
2001-03-01
影响因子：
--
通讯作者：
Stone, EM
中科院分区：
文献类型：
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作者：
Lotery, AJ;Jacobson, SG;Stone, EM
目的：检验 CRB1 基因突变导致莱伯先天性黑蒙 (LCA) 的假设，如果是这样，则描述携带 CRB1 序列变异的 LCA 患者的眼部表型。 患者：从 5 个不同国家确定的 233 名先证者队列中选出 190 名临床诊断为 LCA 的先证者。其余 43 名先证者 (18%) 被排除在外，因为他们在先前鉴定的 LCA 基因中存在序列变异。方法：通过单链构象多态性分析和自动 DNA 测序，对 190 名不相关的 LCA 个体进行 CRB1 基因编码序列突变筛查。结果：190 名先证者中的 21 名（占总队列的 9%） 233 名对照者和 140 名对照者中的 2 名 (1.4%) 在 CRB1 基因中存在氨基酸改变序列变异 (P=0.003)。 结论：在我们的 LCA 患者队列中，在 CRB1 基因中观察到编码序列变异的频率高于其他 5 个已知 LCA 相关基因中的任何一个。目前已在该队列的 233 名受试者中的 64 名 (28%) 中发现了可能引起疾病的序列变异。 临床相关性：分子诊断可以在越来越多的 LCA 患者中确认和澄清诊断。随着基因型数据的积累，可以建立与特定突变相关的临床表型。这将有助于就患者的视觉预后和相关系统异常的可能性向患者提供咨询。
Objectives: To test the hypothesis that mutations in the CRB1 gene cause Leber congenital amaurosis (LCA) and, if so, to describe the ocular phenotype of patients with LCA who harbor CRB1 sequence variations.Patients: One hundred ninety probands with a clinical diagnosis of LCA were selected from a cohort of 233 probands ascertained in 5 different countries. The remaining 43 probands (18%) were excluded because they harbored sequence variations in previously identified LCA genes.Methods: One hundred ninety unrelated individuals with LCA were screened for coding sequence mutations in the CRB1 gene with single-strand conformation polymorphism analysis followed by automated DNA sequencing.Results: Twenty-one of the 190 probands (9% of the total cohort of 233) and 2 (1.4%) of 140 controls harbored amino acid-altering sequence variations in the CRB1 gene (P=.003).Conclusions: in our cohort of patients with LCA, coding sequence variations were observed in the CRB1 gene more frequently than in any of the other 5 known LCA-associated genes. Likely disease-causing sequence variations have now been identified in 64 (28%) of 233 subjects in this cohort.Clinical Relevance: Molecular diagnosis can confirm and clarify the diagnosis in an increasing fraction of patients with LCA. As genotype data accumulate, clinical phenotypes associated with specific mutations may be established. This will facilitate the counseling of patients regarding their visual prognosis and the likelihood of associated systemic anomalies.