Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.
Eur Rev Med Pharmacol Sci. 2021 Jan;25(2):898-905. doi: 10.26355/eurrev_202101_24658.
This article aimed to describe a novel COL4A2 mutation and the phenotypic features of two family members presenting with epilepsy and cortical development malformations.
The first patient is a 65-year-old woman with hematuria and adult-onset seizures. Brain MRI showed closed lip schizencephaly of right lateral sulcus associated with polymicrogyria of the surrounding cortex and areas of subcortical heterotopia. The second patient is a 40-year-old man, her son. He was born post-term with neonatal distress and psychomotor developmental delay with congenital left leg paresis and strabismus, as well as childhood-onset focal motor seizures. Brain MRI showed a right nucleus-capsular porencephalic cavitation with enlargement of the homolateral ventricle and a focal right occipital cortico-subcortical encephalomalacia. A small heterotopic band was also present in the frontal left subcortical region.
We tested both patients with a NGS panel for genetic epilepsies, which evidenced a missense mutation in COL4A2 gene (c.2972G>A, causing the aminoacidic substitution Gly991Glu).
The phenotypic spectrum associated with COL4A2 mutations has not been extensively described in the literature. Testing for COL4A mutations is indicated in patients with malformations of cortical development, particularly in the presence of familial conditions, even in the absence of porencephaly or early hemorrhagic strokes.
本文旨在描述一种新型 COL4A2 突变，并描述两名表现为癫痫和皮质发育畸形的家族成员的表型特征。
第一位患者是一名 65 岁女性，有血尿和成年起病的癫痫。脑部 MRI 显示右侧外侧裂的闭合唇裂脑裂畸形，伴有周围皮质的多微小脑回和皮质下异位区。第二位患者是一名 40 岁男性，是该女性的儿子。他足月出生，有新生儿窒息和精神运动发育迟缓，伴有先天性左侧下肢瘫痪和斜视，以及儿童起病的局灶性运动性癫痫。脑部 MRI 显示右侧核壳脑穿通性脑腔，同侧脑室扩大，右侧枕叶皮质下-皮质脑软化灶。左侧额皮质下区域也存在一个小的异位带。
我们对两名患者进行了遗传性癫痫的 NGS 面板检测，发现 COL4A2 基因存在错义突变（c.2972G>A，导致 Gly991Glu 氨基酸替换）。
COL4A2 突变相关的表型谱在文献中尚未广泛描述。在存在家族性疾病的情况下，即使没有脑穿通畸形或早期出血性中风，COL4A 突变的检测也适用于皮质发育畸形患者，特别是在存在家族性疾病的情况下。
