1例POLA1基因半合变异致X-连锁网状色素异常症的基因诊断  

A case report of genetic testing for X-linked reticulate pigmentary disorder caused by hemizygous mutation of POLA1

作　　者：杨森 孙小瀑 朱惠怡 郭一霖 张亚文 卢成瑜[1] 陈德晖[1] 黄展航 梁欢欣 YANG Sen;SUN Xiaopu;ZHU Huiyi;GUO Yilin;ZHANG Yawen;LU Chengyu;CHEN Dehui;HUANG Zhanhang;LIANG Huanxin(Department of Pediatrics,First Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong 510120,China)

机构地区：[1]广州医科大学附属第一医院儿科,广东广州510120

出　　处：《中国优生与遗传杂志》2022年第3期486-489,共4页Chinese Journal of Birth Health & Heredity

基　　金：国家自然科学基金面上项目(81770063);2022年度广州市科技计划项目,市校(院)联合资助项目。

摘　　要：目的 对临床症状疑似1例X-连锁网状色素异常症(XLRPD)的患儿进行基因诊断。方法 利用高通量测序技术对患者及其父母进行全外显子组测序,筛选候选致病位点,对其家系进行Sanger测序验证。结果 全外显子测序和Sanger测序验证发现家系中患儿X染色体携带POLA1基因半合变异c.1375-354A>G,患儿母亲携带该变异,但无任何临床症状。患儿出现全身皮肤弥漫性黝黑,反复呼吸道感染,前额和双鬓毛发向后上倾斜,生长发育阻滞。结论 结合患儿的临床症状和体征,POLA1基因半合变异c.1375-354 A>G很可能该病的致病基因,符合X连锁遗传规律。为该病的遗传发病机制研究提供了临床资料。Objective To confirm a case report of genetic testing for X-linked reticulate pigmentary disorder(XLRPD)caused by hemizygous mutation of POLA1.Methods The child and his parents were subjected to whole exome sequencing(WES) to identify potential pathogenic variants.Sanger sequencing was performed to confirm the result of WES in available family members.Results A heterozygous mutation c.1375-354 A>G that originated from his mother without any clinical features,was indentified in the POLA1 gene’s intron of the chromosome X by WES,the result was confirmed by Sanger sequencing.The boy patient was characterized by a diffuse hyperpigmentation disorder of the skin,upswept frontal hairline,recurrent respiratory infections and developmental delay.Conclusion The c.1375-354 A>G mutation in the POLA1 gene potentially underlies pathogenic gene mutation in combination with the patient’s manifestation,which conforms to X-linked inheritance.Above result has facilitated to study the genetic pathogenesis.

关 键 词：全外显子测序 家族性X连锁网状色素异常症 POLA1基因 

分 类 号：R725.9[医药卫生—儿科]