Novel TMEM98, MFRP, PRSS56 variants in a large United States high hyperopia and nanophthalmos cohort.
Novel TMEM98, MFRP, PRSS56 variants in a large United States high hyperopia and nanophthalmos cohort.
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美国一个大型高度远视和小眼球队列中的新型TMEM 98、MFRP、PRSS 56变体。
DOI：
10.1038/s41598-020-76725-8
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发表时间：
2020-11-17
影响因子：
4.6
通讯作者：
Hufnagel RB
中科院分区：
文献类型：
--
作者：
Prasov L;Guan B;Ullah E;Archer SM;Ayres BM;Besirli CG;Wiinikka-Buesser L;Comer GM;Del Monte MA;Elner SG;Garnai SJ;Huryn LA;Johnson K;Kamat SS;Lieu P;Mian SI;Rygiel CA;Serpen JY;Pawar HS;Brooks BP;Moroi SE;Richards JE;Hufnagel RB
小眼球是一种罕见的情况，其特征是小的、结构正常的眼睛并由此产生的高度远视。虽然有6个基因(MFRP、PRSS56、MYRF、TMEM98、CRB1、VMD2/BEST1)与这种遗传性疾病有关，但这些基因对小眼球或不太严重的高度远视(相当于≥ + 5.50球镜)的相对贡献还没有完全阐明。我们收集了患有高度远视或纳米眼球( = 眼轴长21.0 mm)的先证者和家系(n = 56例)。在通过质量控制的53个家系中，有10/53(18.8%)的家系通过高通量小组或混合外显子组测序确定了合理的基因诊断。其中TMEM98家系1个(1.9%)，MFRP家系5个(9.4%)，PRSS56家系4个(7.5%)，另有4个家系MFRP或PRSS56有单等位基因相合(7.5%)。一个新的有害的TMEM98变异株(NM_015544.3，C.602G>；C，p.Arg201Pro)，在一个受影响的4个家庭成员中分离出疾病。在MFRP和PRSS56中发现了多个新的错义和移码变体。PRSS56家系比其他已解决的家系更有可能有脉络膜皱褶，而MFRP家系更有可能有视网膜变性。总而言之，这项研究确定了高度远视和纳米眼球患者中纳米眼球基因变异的流行程度，并表明很大一部分病例仍处于单基因编码序列之外。
Nanophthalmos is a rare condition defined by a small, structurally normal eye with resultant high hyperopia. While six genes have been implicated in this hereditary condition (MFRP, PRSS56, MYRF, TMEM98, CRB1,VMD2/BEST1), the relative contribution of these to nanophthalmos or to less severe high hyperopia (≥ + 5.50 spherical equivalent) has not been fully elucidated. We collected probands and families (n = 56) with high hyperopia or nanophthalmos (≤ 21.0 mm axial length). Of 53 families that passed quality control, plausible genetic diagnoses were identified in 10/53 (18.8%) by high-throughput panel or pooled exome sequencing. These include 1 TMEM98 family (1.9%), 5 MFRP families (9.4%), and 4 PRSS56 families (7.5%), with 4 additional families having single allelic hits in MFRP or PRSS56 (7.5%). A novel deleterious TMEM98 variant (NM_015544.3, c.602G>C, p.(Arg201Pro)) segregated with disease in 4 affected members of a family. Multiple novel missense and frameshift variants in MFRP and PRSS56 were identified. PRSS56 families were more likely to have choroidal folds than other solved families, while MFRP families were more likely to have retinal degeneration. Together, this study defines the prevalence of nanophthalmos gene variants in high hyperopia and nanophthalmos and indicates that a large fraction of cases remain outside of single gene coding sequences.
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影响因子：
1.2
作者：
Fuchs, Josefine;Holm, Kari;Fledelius, Hans C
通讯作者：
Fledelius, Hans C
影响因子：
4.4
作者：
Guo, Congcong;Zhao, Zhenni;Fan, Zhigang
通讯作者：
Fan, Zhigang
影响因子：
3.5
作者：
Bejjani, BA;Stockton, DW;Lupski, JR
通讯作者：
Lupski, JR
IBS：用于生物序列呈现和可视化的插画家
DOI：
10.1093/bioinformatics/btv362
发表时间：
2015-10-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Liu W;Xie Y;Ma J;Luo X;Nie P;Zuo Z;Lahrmann U;Zhao Q;Zheng Y;Zhao Y;Xue Y;Ren J
通讯作者：
Ren J
影响因子：
4.5
作者：
Garnai, Sarah J.;Brinkmeier, Michelle L.;Prasovid, Lev
通讯作者：
Prasovid, Lev