HTRA1突变新位点所致的伴有皮质下梗死和白质脑病的常染色体隐性遗传性脑动脉病一家系研究

A family study of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy caused by a new locus of HTRA1 mutation

目的分析并总结HTRA1突变新位点所致的伴有皮质下梗死和白质脑病的常染色体隐性遗传性脑动脉病(CARASIL)一家系临床和遗传学特点。方法对1例CARASIL患者进行病史和临床资料收集,并对部分家系成员进行基因检测,观察其HTRA1位点突变情况。结果先证者表现为认知障碍、可疑腰椎病变、脱发,头颅影像学发现广泛脑白质病变和多发微出血灶。先证者的母亲有精神症状并曾发生脑卒中,六妹有痴呆病史和高血压病。基因检测发现先证者和两个儿子携带HTRA1基因杂合突变c.888C>G(p.I296M),两个儿子已出现脱发。结论c.888C>G(p.I296M)突变位点可能是CARASIL的致病突变新位点。

Objective To analyze the clinical and genetic characteristics of a family of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy(CARASIL)caused by a new locus of HTRA1 mutation.Methods The medical history and clinical data of a patient with CARASIL were collected,and genetic test was performed on some family members to observe the HTRA1 mutation.Results The proband presented with cognitive impairment,suspicious lumbar lesions,and alopecia.Cranial imaging revealed extensive blank brain lesions and multiple microbleeding foci.The mother of the proband had psychiatric symptoms and stroke once,and the sixth younger sister had history of dementia and hypertension.Genetic test revealed that the proband and his two sons carried HTRA1 heterogenic mutation c.888C>G(p.I296M),and the two sons had alopecia.Conclusion The c.888C>G(p.I296M)may be a new pathogenic mutation site of CARASIL.