Novel mutations in Norrie disease gene in Japanese patients with Norrie disease and familial exudative vitreoretinopathy
Novel mutations in Norrie disease gene in Japanese patients with Norrie disease and familial exudative vitreoretinopathy
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DOI：
10.1167/iovs.06-1042
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发表时间：
2007-03-01
影响因子：
4.4
通讯作者：
Hayashi, Kenshi
中科院分区：
文献类型：
--
作者：
Kondo, Hiroyuki;Qin, Minghui;Hayashi, Kenshi
目的.寻找日本家族性渗出性玻璃体视网膜病变（FEVR）和诺里氏病（ND）患者的诺里氏病基因（NDP）突变，并描述突变相关的临床特征。对62例FEVR先证者（31例家族性和31例单纯性）、3例ND先证者及其部分家族成员的血液进行NDP基因所有外显子聚合酶链反应后直接测序。对突变患者的临床症状和体征进行评估。应用白细胞DNA探针检测了3个FEVR家系女性携带者的X染色体失活。在6个家系中发现了4个新的NDP基因突变I18 K、K54 N、R115 L和IVS 2 -1G -> A，以及1个已报道的突变R97 P。这些患者的玻璃体视网膜病变的严重程度各不相同。3例K54 N或R115 L先证者具有FEVR的典型特征，而1例R97 P先证者具有ND的典型特征。IVS 2 -1G -> A的家族表现出ND或FEVR特征。1例I18 K先证者双眼间存在明显的表型异质性。此外，在一个家族中，K54 N突变的女性携带者在视网膜周边出现不同程度的血管异常。X-失活曲线表明，受影响和未受影响的妇女之间的偏斜没有显着差异。这些观察结果表明，NDP基因突变可导致ND和6%的FEVR病例在日本人口。白细胞X-灭活试验可能无法预测受影响女性携带者中存在突变。
PURPOSE. To search for mutations in the Norrie disease gene (NDP) in Japanese patients with familial exudative vitreoretinopathy (FEVR) and Norrie disease (ND) and to delineate the mutation-associated clinical features.METHODS. Direct sequencing after polymerase chain reaction of all exons of the NDP gene was performed on blood collected from 62 probands (31 familial and 31 simplex) with FEVR, from 3 probands with ND, and from some of their family members. The clinical symptoms and signs in the patients with mutations were assessed. X-inactivation in the female carriers was examined in three FEVR families by using leukocyte DNA.RESULTS. Four novel mutations-I18K, K54N, R115L, and IVS2-1G -> A-and one reported mutation, R97P, in the NDP gene were identified in six families. The severity of vitreoretinopathy varied among these patients. Three probands with either K54N or R115L had typical features of FEVR, whereas the proband with R97P had those of ND. Families with IVS2-1G -> A exhibited either ND or FEVR characteristics. A proband with I18K presented with significant phenotypic heterogeneity between the two eyes. In addition, affected female carriers in a family harboring the K54N mutation presented with different degrees of vascular abnormalities in the periphery of the retina. X-inactivation profiles indicated that the skewing was not significantly different between affected and unaffected women.CONCLUSIONS. These observations indicate that mutations of the NDP gene can cause ND and 6% of FEVR cases in the Japanese population. The X-inactivation assay with leukocytes may not be predictive of the presence of a mutation in affected female carriers.