Myelin pathologies are an important cause of multifactorial, e.g., multiple sclerosis, and Mendelian, e.g., leukodystrophy, neurological disorders. CNP encodes a major component of myelin and its CNS expression is exclusive to myelin-forming oligodendrocytes. Deficiency of CNP in mouse causes a lethal white matter neurodegenerative phenotype. However, a corresponding human phenotype has not been described to date. Here, we describe a multiplex consanguineous family from Oman in which multiple affected members display a remarkably consistent phenotype of neuroregression with profound brain white matter loss. A novel homozygous missense variant in CNP was identified by combined autozygome/exome analysis. Immunoblot analysis suggests that this is a null allele in patient fibroblasts, which display abnormal F-actin organization. Our results suggest the establishment of a novel CNP-related hypomyelinating leukodystrophy in humans.

中文翻译：

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CNP缺乏会导致人类严重的低髓性白细胞营养不良。

髓磷脂病理是多因素（例如，多发性硬化症）和孟德尔（例如，白细胞营养不良，神经系统疾病）的重要原因。CNP编码髓磷脂的主要成分，其CNS表达仅对形成髓磷脂的少突胶质细胞有效。小鼠中CNP的缺乏会导致致命的白质神经变性表型。然而，迄今为止尚未描述相应的人表型。在这里，我们描述了一个来自阿曼的多重近亲家庭，其中多个受影响的成员表现出明显的一致的神经退化表型，并伴有严重的脑白质丢失。通过结合的自动酶/外显子组分析鉴定了CNP中的一种新的纯合错义变体。免疫印迹分析表明，这是患者成纤维细胞中无效的等位基因，显示异常的F-肌动蛋白组织。