Unique Variants in OPN1LW Cause Both Syndromic and Nonsyndromic X-Linked High Myopia Mapped to MYP1
Unique Variants in OPN1LW Cause Both Syndromic and Nonsyndromic X-Linked High Myopia Mapped to MYP1
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DOI：
10.1167/iovs.14-16356
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发表时间：
2015-06-01
影响因子：
4.4
通讯作者：
Zhang, Qingjiong
中科院分区：
文献类型：
--
作者：
Li, Jiali;Gao, Bei;Zhang, Qingjiong
目的。 MYP1 是 X 连锁综合征型和非综合征型高度近视的基因座。最近，OPN1LW 中的独特单倍型被发现与 MYP1 映射的 X 连锁综合征高度近视有关。目前的研究旨在测试 OPN1LW 中的此类变异是否也导致映射到 MYP1 的 X 连锁非综合征性高度近视。方法。最初使用全外显子组测序和全基因组测序对先前映射到 MYP1 的家族先证者进行了分析。使用全外显子组测序对其他早发高度近视的先证者进行了分析。 OPN1LW 的变体通过 Sanger 测序进行选择和确认。采用长程PCR和二次PCR确定单倍型和红绿基因阵列的第一个基因。候选变异在家庭成员和对照中得到进一步验证。结果。在映射到 MYP1 的 X 连锁非综合征性高度近视家族中检测到 OPN1LW 中独特的 LVAVA 单倍型。此外，在另外两个 X 连锁高度近视家系中也检测到了 OPN1LW 中的这种单倍型和新的移码突变（c.617_620dup，p.Phe208Argfs*51）。两个家族中高度近视共分离的独特单倍型，在 θ = 0 时最大 LOD 得分为 3.34 和 2.31。这些家族中具有变异的 OPN1LW 是红绿基因阵列中的第一个基因，在 247 名男性对照中不存在。对具有独特单倍型的两个家族的临床数据进行重新评估表明非综合征性高度近视。结论。我们的研究证实了这样的发现：OPN1LW 的独特变异导致了与 MYP1 对应的综合征性和非综合征性 X 连锁高度近视。
PURPOSE. MYP1 is a locus for X-linked syndromic and nonsyndromic high myopia. Recently, unique haplotypes in OPN1LW were found to be responsible for X-linked syndromic high myopia mapped to MYP1. The current study is to test if such variants in OPN1LW are also responsible for X-linked nonsyndromic high myopia mapped to MYP1.METHODS. The proband of the family previously mapped to MYP1 was initially analyzed using whole-exome sequencing and whole-genome sequencing. Additional probands with early-onset high myopia were analyzed using whole-exome sequencing. Variants in OPN1LW were selected and confirmed by Sanger sequencing. Long-range and second PCR were used to determine the haplotype and the first gene of the red-green gene array. Candidate variants were further validated in family members and controls.RESULTS. The unique LVAVA haplotype in OPN1LW was detected in the family with X-linked nonsyndromic high myopia mapped to MYP1. In addition, this haplotype and a novel frameshift mutation (c.617_620dup, p.Phe208Argfs*51) in OPN1LW were detected in two other families with X-linked high myopia. The unique haplotype cosegregated with high myopia in the two families, with a maximum LOD score of 3.34 and 2.31 at theta = 0. OPN1LW with the variants in these families was the first gene in the red-green gene array and was not present in 247 male controls. Reevaluation of the clinical data in both families with the unique haplotype suggested nonsyndromic high myopia.CONCLUSIONS. Our study confirms the findings that unique variants in OPN1LW are responsible for both syndromic and nonsyndromic X-linked high myopia mapped to MYP1.