JAM2基因突变所致常染色体隐性遗传原发性家族性脑钙化一家系研究并文献复习

A family study of autosomal recessive primary familial brain calcification caused by JAM2 gene mutation and literature review

目的报道常染色体隐性遗传原发性家族性脑钙化(PFBC)一家系临床及遗传学特点,提高临床医师对该病认识水平。方法分析2020年1月就诊于河南省人民医院的颅内多发钙化、最终经基因确诊为连接黏附分子2(JAM2)基因突变所致的常染色体隐性遗传PFBC的先证者及其家庭成员的临床、影像及遗传学资料,结合文献分析JAM2基因相关PFBC的临床及影像学特点。结果该家系先证者为32岁男性,首发症状为言语不利及发作性四肢抽搐,伴认知功能下降、肌张力增高;既往有癫痫病史。头颅CT显示双侧小脑、额颞顶叶、皮质下、基底节区及丘脑多发对称性片状、斑片状高密度钙化影。家系中其他成员无相关临床症状。先证者父母头颅CT未见钙化。先证者基因检测结果提示JAM2基因c.685C>T(p.R229*)纯合变异,先证者父母、子女均存在c.685C>T杂合变异,该变异为国外报道过的致病性突变,国内尚未见报道。结论常染色体隐性遗传性PFBC临床上少见,JAM2基因为2020年新发现的PFBC致病基因,对于颅内多发钙化的患者需警惕该基因突变。

Objective To improve the clinician′s recognition of the clinical and molecular characteristics of primary familial brain calcification(PFBC).Methods The detailed clinical information,imaging and molecular characteristics were analyzed in proband and family members of a genetically confirmed autosomal recessive PFBC family.The clinical and imaging features of junctional adhesion molecule 2(JAM2)gene related PFBC were analyzed in combination with the literature review.Results The proband was a 32-year-old man,with slurred speech and paroxysmal limb twitch as the first symptoms,accompanied by cognitive dysfunction,and rigidity in the limbs,with epilepsy in the past.Brain CT showed extensive,symmetrical,and bilateral calcification involving the cerebellum,basal ganglia,thalamus,subcortex and cortex.Other family members showed no related clinical symptoms.Brain CT of the parents of the proband showed no calcification.Gene testing of the proband revealed a homozygous c.685C>T(p.R229*)mutation in JAM2 gene,which has been reported as a pathogenic variation abroad,whereas has not been reported in China.The proband′s parents and children were found with heterozygous c.685C>T(p.R229*)mutation.Conclusions Autosomal recessive inherited PFBC is a rare disease,and JAM2 mutation is a newly discovered pathogenic gene of PFBC in 2020.Patients with intracranial calcification should be alert of JAM2 gene mutation.