单亲二倍体致1例常染色体隐性遗传型Alport综合征  

A patient with autosomal recessive Alport syndrome due to uniparental disomy

作　　者：陈丽珠 黄隽 李政 赵锋 聂晓晶 谷为岳 余自华 Chen Lizhu;Huang Jun;Li Zheng;Zhao Feng;Nie Xiaojing;Gu Weiyue;Yu Zihua(Department of Pediatrics,900 Hospital of the Joint Logistics Support Force,the Chinese People′s Liberation Army,Fuzhou 350025,China;Joy Orient Translational Medicine Research Center Co.,Ltd,Beijing 100035,China)

机构地区：[1]联勤保障部队第九〇〇医院儿科,福州350025 [2]北京智因东方转化医学研究中心有限公司,北京100035

出　　处：《中华实用儿科临床杂志》2020年第24期1905-1907,共3页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金(81270766);福建省社会发展重点课题(2013Y0072);南京军区重大科研课题(14ZX27);南京军区福州总医院院立课题(2016L08)。

摘　　要：分析2016年2月联勤保障部队第九〇〇医院收治1例由单亲二倍体引起的常染色体隐性遗传型Alport综合征的诊断过程。先证者,女,4岁5个月,持续性血尿、蛋白尿2年4个月,血清肌酐、眼耳检查未见异常;其父亲及弟弟持续性血尿,母亲尿检正常;父母系非近亲结婚。基因检测示先证者携带COL4A3基因纯合变异1496G>A(p.G499E);其父亲及弟弟携带相同的杂合变异,母亲未携带该变异。生物信息学分析示COL4A3基因1496G>A为致病变异。免疫荧光定量PCR和染色体微阵列分析证实先证者在染色体2p25.3-2q37.3为单亲二倍体,该片段包含COL4A3基因。先证者诊断为单亲二倍体引起的常染色体隐性遗传型Alport综合征,提示在父母为非近亲结婚的家族性血尿患者中检测出COL4A3基因纯合致病变异时应考虑单亲二倍体。This report describes a girl with autosomal recessive Alport syndrome(ARAS)due to segmental paternal isodisomy at 900 Hospital of the Joint Logistics Support Force,the Chinese People′s Liberation Army in February 2016.The girl was from a non-consanguineous family at age of 4 years and 5 months old.Her urine revealed a persistent microhematuria and proteinuria for 2 years and 4 months.Her renal function,as observed by serum creatinine,was normal,her ophthalmologic and otologic evaluations showed normality as well.Microhematuia was found in both her father and sibling,whereas neither was detected in her mother.Molecular analysis for familial hematuria-associated genes revealed a homozygous variant,1496G>A(p.G499E),in the COL4A3 gene in the girl,the same heterozygous variant in both her father and sibling,but neither in her mother.Bioinformatics strongly suggests that the variant may be pathogenic.Fluorescence quantitative polymerase chain reaction and chromosomal microarray analysis revealed a segmental paternal isodisomy in the chromosome region 2p25.3-2q37.3,where the COL4A3 gene locates.The girl was diagnosed as ARAS caused by segmental paternal isodisomy.The result suggests that uniparental disomy should be considered when the cases with familial hematuria from non-consanguineous parents manifest homozygous variant of the COL4A3 gene.

关 键 词：单亲二倍体 常染色体隐性遗传型Alport综合征 家族性血尿 COL4A3基因 

分 类 号：R726.9[医药卫生—儿科]