Exome analysis identified a novel mutation in the RBP4 gene in a consanguineous pedigree with retinal dystrophy and developmental abnormalities.
Exome analysis identified a novel mutation in the RBP4 gene in a consanguineous pedigree with retinal dystrophy and developmental abnormalities.
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DOI：
10.1371/journal.pone.0050205
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ayyagari R
中科院分区：
文献类型：
--
作者：
Cukras C;Gaasterland T;Lee P;Gudiseva HV;Chavali VR;Pullakhandam R;Maranhao B;Edsall L;Soares S;Reddy GB;Sieving PA;Ayyagari R
色素性视网膜炎（RP）是视网膜变性的常见形式，其特征在于光感受器变性和视网膜色素上皮（RPE）萎缩，导致视野和视力丧失。外显子组测序鉴定了编码视黄醇结合蛋白4（RBP4）的基因中的一种新的纯合剪接位点变体（c.111+1G>A）。在一个欧洲血统的八成员血缘家系中，这种变化与早发性、进行性和严重的常染色体隐性视网膜色素变性（arRP）分离。此外，1例患者表现出发育异常，包括动脉导管未闭和脉络膜视网膜和虹膜缺损。第二名患者从年轻时就出现痤疮，并持续到第五个十年。这两名患者的血清中RBP4水平检测不到，这表明该突变导致mRNA或蛋白质不稳定，导致无效表型。此外，患者表现出严重的维生素A缺乏症，血清视黄醇水平降低。循环甲状腺素运载蛋白水平正常。这项研究确定了RBP4剪接位点的变化是该家系RP的原因。视网膜变性患者中发育异常和严重痤疮的存在可能表明调节维生素A吸收、运输和代谢的基因的参与。
Retinitis Pigmentosa (RP) is a common form of retinal degeneration characterized by photoreceptor degeneration and retinal pigment epithelium (RPE) atrophy causing loss of visual field and acuities. Exome sequencing identified a novel homozygous splice site variant (c.111+1G>A) in the gene encoding retinol binding protein 4 (RBP4). This change segregated with early onset, progressive, and severe autosomal recessive retinitis pigmentosa (arRP) in an eight member consanguineous pedigree of European ancestry. Additionally, one patient exhibited developmental abnormalities including patent ductus arteriosus and chorioretinal and iris colobomas. The second patient developed acne from young age and extending into the 5th decade. Both patients had undetectable levels of RBP4 in the serum suggesting that this mutation led to either mRNA or protein instability resulting in a null phenotype. In addition, the patients exhibited severe vitamin A deficiency, and diminished serum retinol levels. Circulating transthyretin levels were normal. This study identifies the RBP4 splice site change as the cause of RP in this pedigree. The presence of developmental abnormalities and severe acne in patients with retinal degeneration may indicate the involvement of genes that regulate vitamin A absorption, transport and metabolism.
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影响因子：
1.4
作者：
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通讯作者：
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作者：
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通讯作者：
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