A novel mutation and phenotypes in phosphodiesterase 6 deficiency.
A novel mutation and phenotypes in phosphodiesterase 6 deficiency.
复制标题
DOI：
10.1016/j.ajo.2008.06.017
复制
发表时间：
2008-11
影响因子：
4.2
通讯作者：
Allikmets, Rando
中科院分区：
文献类型：
--
作者：
Tsang, Stephen H.;Tsui, Irena;Chou, Chai Lin;Zernant, Jana;Haamer, Eneli;Iranmanesh, Reza;Tosi, Joaquin;Allikmets, Rando
建立视网膜色素变性(RP)分子诊断的系统方法，并报道基于磷酸二酯酶6(PDE6)的RP突变的新的基因-表型相关性。一系列回顾性病例的临床和分子研究。我们用常染色体隐性RP芯片筛选了40例无关的RP患者。对PDE6缺乏引起的RP个体进行遗传分离和表型分析。在32%的患者中发现了与疾病相关的等位基因。2名先证者(5%)有PDE6突变。第一个先证者是PDE6A(MIM#180071)中已知的R102C和N216S等位基因的复合杂合子。家系分析确定N216S变异是良性的，直接测序发现了一个新的等位基因S303C。第二个先证者在PDE6B基因(MIM#180072)中有纯合子D600N突变。PDE6缺陷患者的视力在20/40~20/200之间。临床研究显示PDE6缺乏的患者出现不寻常的玻璃体黄斑牵引、黄斑囊样水肿、黄斑萎缩和环形强荧光。如此广泛的玻璃体视网膜变性不是光感受器特异性酶缺乏的特征。高通量DNA微阵列芯片可以与临床成像结合使用，以准确地确定RP患者的特征。随着基因治疗的出现，识别RP的精确突变可能成为护理的标准。
To develop a systematic approach for the molecular diagnosis of retinitis pigmentosa (RP) and to report new genotype-phenotype correlations for phosphodiesterase 6 (PDE6) based RP mutations. Clinical and molecular studies on a retrospective case series. We screened 40 unrelated RP patients with an autosomal recessive RP microarray. Individuals with RP caused by PDE6 deficiency underwent genetic segregation and phenotype analysis. A disease-associated allele was identified in 32% of patients. Two probands (5%) had PDE6 mutations. The first proband was a compound heterozygote for known R102C and N216S alleles in PDE6A (MIM#180071). Pedigree analysis determined that the N216S variant was benign and direct sequencing discovered a novel, S303C allele. The second proband had a homozygous D600N mutation in the PDE6B gene (MIM#180072). Visual acuities of PDE6 deficient patients ranged from 20/40 to 20/200. Clinical studies showed unusual vitreomacular traction, cystoid macular edema, macular atrophy, and ring hyperfluorescence in PDE6 deficient patients. Such extensive vitreoretinal degeneration is not characteristic of photoreceptor-specific enzyme deficiencies. High throughput DNA microarray chips can be used in combination with clinical imaging to precisely characterize patients with RP. Identifying the precise mutation in RP may become the standard of care as gene therapy emerges.
登录
查看更多内容
DOI：
10.1089/109065700316408
发表时间：
2000-03-01
期刊：
GENETIC TESTING
影响因子：
--
作者：
Kurg, A;Tonisson, N;Metspalu, A
通讯作者：
Metspalu, A
影响因子：
2.5
作者：
Gargini, Claudia;Terzibasi, Eva;Strettoi, Enrica
通讯作者：
Strettoi, Enrica
影响因子：
4
作者：
Koenekoop, Robert K.;Lopez, Irma;Cremers, Frans P. M.
通讯作者：
Cremers, Frans P. M.
影响因子：
5.1
作者：
Jomary, C;Vincent, KA;Jones, SE
通讯作者：
Jones, SE
影响因子：
4.2
作者：
Stone, Edwin M.
通讯作者：
Stone, Edwin M.