COL4A1/COL4A2 and inherited platelet disorder gene variants in fetuses showing intracranial hemorrhage.
COL4A1/COL4A2 and inherited platelet disorder gene variants in fetuses showing intracranial hemorrhage.
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作者：
COL4A1/COL4A2基因变异已在胎儿颅内出血（ICH）病例中报道，但其患病率和特征尚未在大量胎儿中确定。胎儿新生儿同种免疫性血小板减少症是获得性脑出血的主要因素，但遗传性血小板障碍（IPD）基因变异导致血小板减少症的患病率和特征尚不清楚。在此，我们筛选了大量ICH胎儿的COL4A1/COL4A2和IPD基因。首先对194个连续的脑出血胎儿进行COL4A1/COL4A2变异筛查。我们手动整理了64个与IPD相关的基因列表，并使用来自101个这些胎儿的外显子组测序数据，在COL4A1/COL4A2阴性胎儿中研究了它们。在36例（19%）胎儿中鉴定出COL4A1/COL4A2基因的致病变异。在可获得父母DNA的32个胎儿中，有70%是从头开始的。两种巨核生成基因（MPL和MECOM基因）的致病变异在两个家族复发和严重的胎儿脑出血，具有不同的神经外病理特征。我们的研究强调了胎儿脑出血的遗传异质性，以及在胎儿脑出血的病因调查中筛查COL4A1/COL4A2和IPD基因的必要性，以便进行适当的遗传咨询。
Variants of COL4A1/COL4A2 genes have been reported in fetal intracranial hemorrhage (ICH) cases but their prevalence and characteristics have not been established in a large series of fetuses. Fetal neonatal alloimmune thrombocytopenia is a major acquired ICH factor but the prevalence and characteristics of inherited platelet disorder (IPD) gene variants leading to thrombocytopenia are unknown. Herein, we screened COL4A1/COL4A2 and IPD genes in a large series of ICH fetuses. A cohort of 194 consecutive ICH fetuses were first screened for COL4A1/COL4A2 variants. We manually curated a list of 64 genes involved in IPD and investigated them in COL4A1/COL4A2 negative fetuses, using exome sequencing data from 101 of these fetuses. Pathogenic variants of COL4A1/COL4A2 genes were identified in 36 fetuses (19%). They occurred de novo in 70% of the 32 fetuses for whom parental DNA was available. Pathogenic variants in two megakaryopoiesis genes (MPL and MECOM genes) were identified in two families with recurrent and severe fetal ICH, with variable extraneurological pathological features. Our study emphasizes the genetic heterogeneity of fetal ICH and the need to screen both COL4A1/COL4A2 and IPD genes in the etiological investigation of fetal ICH to allow proper genetic counseling.
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遗传性血小板增多症中 MPL R102P 突变的鉴定。
影响因子：
5.2
作者：
Bellanné-Chantelot C;Mosca M;Marty C;Favier R;Vainchenker W;Plo I
通讯作者：
Plo I
影响因子：
2.9
作者：
Colin, E.;Sentilhes, L.;Bonneau, D.
通讯作者：
Bonneau, D.
影响因子：
4.6
作者：
Johnson B;Doak R;Allsup D;Astwood E;Evans G;Grimley C;James B;Myers B;Stokley S;Thachil J;Wilde J;Williams M;Makris M;Lowe GC;Wallis Y;Daly ME;Morgan NV;UK GAPP Study Group
通讯作者：
UK GAPP Study Group
影响因子：
7.5
作者：
Germeshausen, Manuela;Ancliff, Phil;Ballmaier, Matthias
通讯作者：
Ballmaier, Matthias
影响因子：
3
作者：
Bouchghoul, Hanane;Quelin, Chloe;Martinovic, Jelena
通讯作者：
Martinovic, Jelena