Lenge Matteo, Marini Carla, Canale Edoardo, Napolitano Antonio, De Masi Salvatore, Trivisano Marina, Mei Davide, Longo Daniela, Rossi Espagnet Maria Camilla, Lucenteforte Ersilia, Barba Carmen, Specchio Nicola, Guerrini Renzo
Child Neurology Unit and Laboratories, Neuroscience Department, Children's Hospital A. Meyer - University of Florence, 50139 Florence, Italy.
Functional and Epilepsy Neurosurgery Unit, Neurosurgery Department, Children's Hospital A. Meyer - University of Florence, 50139 Florence, Italy.
Cereb Cortex. 2020 Oct 1;30(11):6039-6050. doi: 10.1093/cercor/bhaa177.
Protocadherin-19 (PCDH19) is a calcium dependent cell-adhesion molecule involved in neuronal circuit formation with prevalent expression in the limbic structures. PCDH19-gene mutations cause a developmental encephalopathy with prominent infantile onset focal seizures, variably associated with intellectual disability and autistic features. Diagnostic neuroimaging is usually unrevealing. We used quantitative MRI to investigate the cortex and white matter in a group of 20 PCDH19-mutated patients. By a statistical comparison between quantitative features in PCDH19 brains and in a group of age and sex matched controls, we found that patients exhibited bilateral reductions of local gyrification index (lGI) in limbic cortical areas, including the parahippocampal and entorhinal cortex and the fusiform and lingual gyri, and altered diffusivity features in the underlying white matter. In patients with an earlier onset of seizures, worse psychiatric manifestations and cognitive impairment, reductions of lGI and diffusivity abnormalities in the limbic areas were more pronounced. Developmental abnormalities involving the limbic structures likely represent a measurable anatomic counterpart of the reduced contribution of the PCDH19 protein to local cortical folding and white matter organization and are functionally reflected in the phenotypic features involving cognitive and communicative skills as well as local epileptogenesis.
原钙黏蛋白-19（PCDH19）是一种钙依赖性细胞黏附分子，参与神经回路形成，在边缘结构中普遍表达。PCDH19基因突变会导致一种发育性脑病，其特征为婴儿期起病的局灶性癫痫发作，常伴有智力残疾和自闭症特征。诊断性神经影像学检查通常无明显异常。我们使用定量磁共振成像（MRI）对一组20名PCDH19基因突变患者的皮质和白质进行了研究。通过对PCDH19基因突变患者大脑与一组年龄和性别匹配的对照者的定量特征进行统计学比较，我们发现患者边缘皮质区域的局部脑回指数（lGI）出现双侧降低，这些区域包括海马旁回和内嗅皮质以及梭状回和舌回，并且其下方白质的扩散特性也发生了改变。在癫痫发作起病较早、精神症状较重和认知功能受损的患者中，边缘区域的lGI降低和扩散异常更为明显。涉及边缘结构的发育异常可能是PCDH19蛋白对局部皮质折叠和白质组织贡献减少的可测量解剖学对应物，并且在涉及认知和沟通技能以及局部癫痫发生的表型特征中得到功能反映。
