Dominant Leber congenital amaurosis, cone-rod degeneration, and retinitis pigmentosa caused by mutant versions of the transcription factor CRX
Dominant Leber congenital amaurosis, cone-rod degeneration, and retinitis pigmentosa caused by mutant versions of the transcription factor CRX
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DOI：
10.1002/humu.1226
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发表时间：
2001-01-01
期刊：
影响因子：
3.9
通讯作者：
Dryja, TP
中科院分区：
文献类型：
--
作者：
Rivolta, C;Berson, EL;Dryja, TP
我们总结了18个与先天性黑蒙（先天性视网膜盲）、视锥细胞、视杆细胞变性或视网膜色素变性相关的CRX基因突变。除了一个明显无效的等位基因与表型不明确相关（密码子9的移码）外，所有CRX突变似乎都是完全外显的，并在杂合子中引起疾病。这些显性等位基因分为两类。一组是错义突变和短的框内缺失;第二组是移码突变，所有这些都在最后一个外显子中。所有这些显性突变都有可能产生稳定的mRNA。错义组中的突变优先影响保守的同源框（密码子39-98），并且所有移码突变使同源结构域保持完整，但改变羧基末端由密码子284-295编码的OTX基序。我们无法发现疾病类型（先天性黑蒙与视锥、视杆变性或视网膜色素变性）和突变类型（错义与移码）之间的任何相关性。18个突变中有4个（约占20%）是新生突变，所有这些突变都是在孤立的Leber先天性黑蒙病例中发现的。显性CRX突变与智力迟钝或发育迟缓无关，而智力迟钝或发育迟缓有时在其他基因引起的Leber先天性黑蒙中发现。关于潜在的未来治疗的影响进行了讨论。2001年，《突变》18：488-498。(C)2001 Wiley-Liss，Inc.
We summarize 18 mutations in the human CRX gene that have been associated with Leber congenital amaurosis (congenital retinal blindness), cone,rod degeneration, or retinitis pigmentosa. Except for one obviously null allele not definitely associated with a phenotype (a frameshift in codon 9), all CRX mutations appear to be completely penetrant and cause disease in heterozygotes. These dominant alleles fall into two categories. In one group are missense mutations and short, in-frame deletions; in the second group are frameshift mutations, all of which are in the last exon. All of these dominant mutations are likely to produce stable mRNA that is translated. Mutations in the missense group preferentially affect the conserved homeobox (codons 39-98), and all frameshift mutations leave the homeodomain intact but alter the OTX motif encoded by codons 284-295 at the carboxy terminus. We could not uncover any correlation between type of disease (congenital amaurosis vs. cone,rod degeneration or retinitis pigmentosa) and the type of mutation (missense vs. frameshift). Four of the 18 mutations (similar to 20%) were de novo mutations, and all of these were found in isolate cases of Leber congenital amaurosis. Dominant CRX mutations have not been associated with mental retardation or developmental delay that has sometimes been found in Leber congenital amaurosis caused by other genes. Implications regarding potential future therapies are discussed. Hum Mutat 18:488-498, 2001. (C) 2001 Wiley-Liss, Inc.