Novel insights into the molecular pathogenesis of CYP4V2-associated Bietti's retinal dystrophy.
Novel insights into the molecular pathogenesis of CYP4V2-associated Bietti's retinal dystrophy.
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DOI：
10.1002/mgg3.109
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发表时间：
2015-01
影响因子：
2
通讯作者：
Koenekoop, Robert K.
中科院分区：
文献类型：
--
作者：
Astuti, Galuh D. N.;Sun, Vincent;Bauwens, Miriam;Zobor, Ditta;Leroy, Bart P.;Omar, Amer;Jurklies, Bernhard;Lopez, Irma;Ren, Huanan;Yazar, Volkan;Hamel, Christian;Kellner, Ulrich;Wissinger, Bernd;Kohl, Susanne;De Baere, Elfride;Collin, Rob W. J.;Koenekoop, Robert K.
Bietti晶体营养不良（BCD）是一种罕见的常染色体隐性视网膜退行性疾病，与CYP 4V 2突变相关。在这项研究中，我们描述了19个无关的BCD患者从五个国际视网膜营养不良诊所招募的遗传和临床研究结果。患者接受眼科检查，并通过桑格测序和定量聚合酶链反应（qPCR）拷贝数变异筛查进行CYP 4 V2突变筛查。在10/19例患者中发现了8种CYP 4V 2突变，包括3例仅检测到单等位基因突变的患者。鉴定了四个新的突变：c.604G>A; p.（Glu202Lys），c.242C>G; p.（Thr81Arg），c.604+4A>G; p. (?),和c.1249dup; p.（Thr417Asnfs*2）。此外，我们确定了一个杂合子父系遗传基因组缺失至少3.8 Mb，包括完整的CYP 4V 2基因和其他几个基因，这是新的。临床上，患者表现出表型变异性，主要表现为脉络膜硬化、血管变细和不同严重程度的结晶沉积。据我们所知，我们的研究报告了第一个杂合CYP 4V 2缺失，因此是BCD的一种新的突变机制。我们的研究结果强调了在BCD中拷贝数筛选的重要性。最后，CYP 4V 2阴性患者与CYP 4V 2阳性患者的表型无法区分，这可能表明存在CYP 4V 2编码区以外的突变或基因座异质性，这是迄今为止尚未报道的。
Bietti's crystalline dystrophy (BCD) is a rare, autosomal recessive retinal degenerative disease associated with mutations in CYP4V2. In this study, we describe the genetic and clinical findings in 19 unrelated BCD patients recruited from five international retinal dystrophy clinics. Patients underwent ophthalmic examinations and were screened for CYP4V2 mutations by Sanger sequencing and quantitative polymerase chain reaction (qPCR) copy number variation screening. Eight CYP4V2 mutations were found in 10/19 patients, including three patients in whom only monoallelic mutations were detected. Four novel mutations were identified: c.604G>A; p.(Glu202Lys), c.242C>G; p.(Thr81Arg), c.604+4A>G; p.(?), and c.1249dup; p.(Thr417Asnfs*2). In addition, we identified a heterozygous paternally inherited genomic deletion of at least 3.8 Mb, encompassing the complete CYP4V2 gene and several other genes, which is novel. Clinically, patients demonstrated phenotypic variability, predominantly showing choroidal sclerosis, attenuated vessels, and crystalline deposits of varying degrees of severity. To our knowledge, our study reports the first heterozygous CYP4V2 deletion and hence a novel mutational mechanism underlying BCD. Our results emphasize the importance of copy number screening in BCD. Finally, the identification of CYP4V2-negative patients with indistinguishable phenotypes from CYP4V2-positive patients might suggest the presence of mutations outside the coding regions of CYP4V2, or locus heterogeneity, which is unreported so far.
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影响因子：
1.4
作者：
Marmor, M. F.;Fulton, A. B.;Bach, M.
通讯作者：
Bach, M.
影响因子：
14.9
作者：
Desmet FO;Hamroun D;Lalande M;Collod-Béroud G;Claustres M;Béroud C
通讯作者：
Béroud C
影响因子：
2.9
作者：
CHUNG, DW;FUJIKAWA, K;DAVIE, EW
通讯作者：
DAVIE, EW
影响因子：
4
作者：
Lin, J;Nishiguchi, KM;Miyake, Y
通讯作者：
Miyake, Y
影响因子：
4.4
作者：
Collin, Rob W. J.;van den Born, L. Ingeborgh;Cremers, Frans P. M.
通讯作者：
Cremers, Frans P. M.