原发性家族性脑钙化是一组以双侧对称性脑钙化为影像学特征，伴多种神经、精神症状的神经系统遗传性疾病。现共有4个致病基因SLC20A2、PDGFRB、PDGFB和XPR1被鉴定，均为常染色体显性遗传致病，仍有不少该病家系的致病基因尚不明确。本团队前期收集到10个十分罕见的患者父母近亲婚配的原发性家族性脑钙化家系，其中5个家系内有兄弟姐妹多人患病，父母头颅CT未见脑钙化，提示存在常染色体隐性遗传的新致病基因。前期通过纯合子定位及全基因组测序，我们在家系A中发现1个很可能的新致病基因X基因（文章尚未发表，基因名以X替代），目前正在其他家系及患者中进行验证，并拟通过建立疾病细胞模型和动物模型对其进行进一步的功能研究。下一步我们将结合纯合子定位、全基因组测序等技术鉴定其他家系的致病基因，同时对X基因及可能新发现的其他致病基因进行相关功能研究，进一步揭示该病的发病机制，为该病的防治及药物研发打下基础。

Primary familial brain calcification is one kind of neurological inherited disease radiologically characterized by bilateral brain calcifications and clinically characterized by an insidious and progressive development of movement disorders, cognitive decline, and psychiatric symptoms. To date, there were four autosomal dominant inherited causative genes - SLC20A2, PDGFRB, PDGFB and XPR1 identified, which improved our understanding to the pathogenesis of this disease. However, there were still some pedigrees whose causative genes were unknown. Recently we collected 10 consanguineous pedigrees with primary familial brain calcification. There are several affected siblings in 5 pedigrees and these parents’ CT scan showed no brain calcification. These clues indicate that there are autosomal recessive inherited causative genes existed in these pedigrees. We have found a probable causative gene - X gene in Pedigree A by using homozygosity mapping and whole-genome sequencing. We are trying to sequence X gene in other pedigrees and patients. Functional studies of X gene are also going to be done. In the following steps, we plan to identify the causative genes of other pedigrees. Further functional studies of X gene and other newly identified causative genes may help us to know further pathogenesis of primary familial brain calcification. This will contribute to the prevention, diagnosis and treatment of primary familial brain calcification.