Moyamoya血管病(MA)是一种罕见的脑血管疾病,其特征是颈内动脉进行性闭塞。其病因尚不确定,但是遗传背景似乎很可能,鉴于MA家族率高。探讨1例14岁男性患者颅骨融合和青少年烟雾病的病因,我们进行了阵列-比较基因组杂交,揭示了染色体区域1p32p31中8.5Mb的从头间质缺失。缺失涉及34个蛋白质编码基因,包括NF1A,其单倍体功能不全被认为是1p32-p31染色体缺失综合征表型的主要原因(OMIM613735)。我们的病人也有一个删除的FOX基因家族的转录因子的FOXD3,在神经c细胞的生长和分化中起着重要作用。由于小鼠FOXD3-/-模型显示颅面异常和颈总动脉形态异常,可以假设FOXD3与我们患者观察到的颅面和血管缺损的发病机制有关.为了支持我们的假设,我们在文献中发现了另一名MA综合征型患者,其缺失涉及另一个FOX基因(FOXC1).除了描述我们病人的临床病史,我们回顾了所有有关其他1p32p31缺失患者的可用文献,包括破译数据库中的病例,我们还回顾了与MA相关的遗传疾病,这是诊断MA综合征形式的有用指南。
Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterised by the progressive occlusion of the internal carotid artery. Its aetiology is uncertain, but a genetic background seems likely, given the high MA familial rate. To investigate the aetiology of craniosynostosis and juvenile moyamoya in a 14-year-old male patient, we performed an array-comparative genomic hybridisation revealing a de novo interstitial deletion of 8.5 Mb in chromosome region 1p32p31. The deletion involved 34 protein coding genes, including NF1A, whose haploinsufficiency is indicated as being mainly responsible for the 1p32-p31 chromosome deletion syndrome phenotype (OMIM 613735). Our patient also has a deleted
FOXD3 of the FOX gene family of transcription factors, which plays an important role in neural crest cell growth and differentiation. As the murine
FOXD3-/- model shows craniofacial anomalies and abnormal common carotid artery morphology, it can be hypothesised that
FOXD3 is involved in the pathogenesis of the craniofacial and vascular defects observed in our patient. In support of our assumption, we found in the literature another patient with a syndromic form of MA who had a deletion involving another FOX gene (FOXC1). In addition to describing the clinical history of our patient, we have reviewed all of the available literature concerning other patients with a 1p32p31 deletion, including cases from the Decipher database, and we have also reviewed the genetic disorders associated with MA, which is a useful guide for the diagnosis of syndromic form of MA.