PDF(Pubmed)
Abstract：
UNASSIGNED: The underlying molecular defects of congenital hydrocephalus are heterogeneous and many isolated forms of hydrocephalus remain unsolved at the molecular level. Congenital hydrocephalus in males associated with agenesis of the corpus callosum is a notable characteristic of L1CAM gene which is by far the most common genetic etiology of congenital hydrocephalus.
UNASSIGNED: Sequencing of the L1CAM gene on 25 male patients/fetuses who had been presented with hydrocephalus revealed 6 patients and two fetuses with different hemizygous pathogenic variants. Our study identified 4 novel variants and 4 previously reported. The detection rate was 32%, and all the variants were shown to be maternally inherited. Nonsense variants were detected in 3 patients, while missense variants were detected in 2 patients. Frameshift, silent, and splicing variant, each was detected in 1 patient. The clinical manifestations of the patients are in line with those frequently observed including communicating hydrocephalus and agenesis of the corpus callosum. Moreover, rippled ventricles with subdural collection and asymmetry of ventricles after shunt operation were seen in 1 patient and 2 patients, respectively. In addition, abnormal basal ganglia were found in 4 patients which seems to be an additional distinct new finding. We also describe a patient with novel nonsense variant with the rare association of Hirschsprung\'s disease. This patient displayed additionally multiple porencephalic cysts and encephalomalacia secondary to hemorrhage due to repeated infections after shunt operation. The patients with the missense variants showed long survival, while those with truncating variants showed poor prognosis.
UNASSIGNED: This report adds knowledge of novel pathogenic variants to the L1CAM variant database. Furthermore, we evaluated the clinical and imaging data of these patients.
UNASSIGNED: Sequencing of the L1CAM gene on 25 male patients/fetuses who had been presented with hydrocephalus revealed 6 patients and two fetuses with different hemizygous pathogenic variants. Our study identified 4 novel variants and 4 previously reported. The detection rate was 32%, and all the variants were shown to be maternally inherited. Nonsense variants were detected in 3 patients, while missense variants were detected in 2 patients. Frameshift, silent, and splicing variant, each was detected in 1 patient. The clinical manifestations of the patients are in line with those frequently observed including communicating hydrocephalus and agenesis of the corpus callosum. Moreover, rippled ventricles with subdural collection and asymmetry of ventricles after shunt operation were seen in 1 patient and 2 patients, respectively. In addition, abnormal basal ganglia were found in 4 patients which seems to be an additional distinct new finding. We also describe a patient with novel nonsense variant with the rare association of Hirschsprung\'s disease. This patient displayed additionally multiple porencephalic cysts and encephalomalacia secondary to hemorrhage due to repeated infections after shunt operation. The patients with the missense variants showed long survival, while those with truncating variants showed poor prognosis.
UNASSIGNED: This report adds knowledge of novel pathogenic variants to the L1CAM variant database. Furthermore, we evaluated the clinical and imaging data of these patients.
摘要：
■先天性脑积水的潜在分子缺陷是异质的，许多孤立形式的脑积水在分子水平上仍未解决。与call体发育不全相关的男性先天性脑积水是L1CAM基因的显着特征，L1CAM基因是迄今为止最常见的先天性脑积水的遗传病因。
■对25例患有脑积水的男性患者/胎儿进行L1CAM基因测序，发现6例患者和2例胎儿具有不同的半合子致病变异。我们的研究确定了4个新的变体和4个以前报道的。检出率为32%,所有的变异都被证明是母系遗传的。在3例患者中检测到无义变异，而在2例患者中检测到错义变异。Frameshift,沉默,和剪接变体，在1例患者中检测到每一例.患者的临床表现与经常观察到的临床表现一致，包括交通性脑积水和call体发育不全。此外，1例患者和2例患者在分流手术后观察到具有硬膜下集合和心室不对称的波纹心室，分别。此外,在4例患者中发现了异常的基底神经节，这似乎是另一个独特的新发现。我们还描述了一个具有新的无义变体的患者，该变体与Hirschsprung病的罕见关联。由于分流手术后反复感染，该患者还表现出多发的脑后部囊肿和继发于出血的脑软化。具有错义变异的患者显示出长期的生存,而那些具有截断变异的患者预后较差。
■本报告为L1CAM变异数据库增加了新的致病变异的知识。此外，我们评估了这些患者的临床和影像学资料.
■对25例患有脑积水的男性患者/胎儿进行L1CAM基因测序，发现6例患者和2例胎儿具有不同的半合子致病变异。我们的研究确定了4个新的变体和4个以前报道的。检出率为32%,所有的变异都被证明是母系遗传的。在3例患者中检测到无义变异，而在2例患者中检测到错义变异。Frameshift,沉默,和剪接变体，在1例患者中检测到每一例.患者的临床表现与经常观察到的临床表现一致，包括交通性脑积水和call体发育不全。此外，1例患者和2例患者在分流手术后观察到具有硬膜下集合和心室不对称的波纹心室，分别。此外,在4例患者中发现了异常的基底神经节，这似乎是另一个独特的新发现。我们还描述了一个具有新的无义变体的患者，该变体与Hirschsprung病的罕见关联。由于分流手术后反复感染，该患者还表现出多发的脑后部囊肿和继发于出血的脑软化。具有错义变异的患者显示出长期的生存,而那些具有截断变异的患者预后较差。
■本报告为L1CAM变异数据库增加了新的致病变异的知识。此外，我们评估了这些患者的临床和影像学资料.
