Cerebral palsy in siblings caused by compound heterozygous mutations in the gene encoding protein C
Cerebral palsy in siblings caused by compound heterozygous mutations in the gene encoding protein C
复制标题
DOI：
10.1111/j.1469-8749.2010.03618.x
复制
发表时间：
2010-05-01
影响因子：
3.8
通讯作者：
Jardine, Philip E.
中科院分区：
文献类型：
--
作者：
Fong, Choong Yi;Mumford, Andrew D.;Jardine, Philip E.
我们报告两姐妹篇广泛的双侧脑室周围出血性梗死（PVHI）造成脑性瘫痪（CP）。姐姐在20个月时出现皮质性视盲、痉挛性双瘫和暴发性紫癜。妹妹3天大时出现呼吸暂停和多灶性癫痫发作。她随后在2岁时出现了全面发育迟缓、皮质性视盲、痉挛性四肢瘫痪、癫痫和暴发性紫癜。两个兄弟姐妹的神经成像显示双侧PVHI与双侧脑髓内静脉血栓形成一致，姐姐发生在妊娠28周以下，妹妹发生在出生前后。在最后一次随访时，姐姐（13岁）出现粗大运动功能分类系统（GMFCS）II级痉挛性双瘫，妹妹（10岁）出现GMFCS IV级痉挛性四肢瘫。两姐妹篇均显示血浆蛋白C抗原部分定量降低和血浆蛋白C抗凝活性严重定性降低。他们在蛋白C基因（PROC）的两个独立的突变杂合。CP没有其他危险因素。据我们所知，这是第一个家庭报告的复合杂合PROC突变作为家族性CP的可能遗传原因。这份报告增加了已知的单基因原因的CP。
We report two sisters with extensive bilateral periventricular haemorrhagic infarction (PVHI) causing cerebral palsy (CP). The older sister presented at 20 months with cortical visual blindness, spastic diplegia, and purpura fulminans. The younger sister presented aged 3 days old with apnoeas and multifocal seizures. She subsequently had global developmental delay, cortical visual blindness, spastic quadriplegia, epilepsy, and purpura fulminans at age 2 years. Neuroimaging of both siblings showed bilateral PVHI consistent with bilateral cerebral intramedullary venous thrombosis occurring at under 28 weeks' gestation for the older sister and around time of birth for the younger sister. At latest follow-up, the older sister (13y) has spastic diplegia at Gross Motor Function Classification System (GMFCS) level II, and the younger sister (10y) has spastic quadriplegia at GMFCS level IV. Both sisters showed partial quantitative reduction in plasma protein C antigen and severe qualitative reduction in plasma protein C anticoagulant activity. They were heterozygous for two independent mutations in the protein C gene (PROC). There was no other risk factor for CP. To our knowledge, this is the first family reported with compound heterozygous PROC mutations as the likely genetic cause of familial CP. This report adds to the list of known monogenic causes of CP.