GUCY2D基因复合杂合致Leber氏先天性黑蒙合并妊娠1例  

A case of compound heterozygosity in the GUCY2D gene causes Leber's congenital amaurosis combined with pregnancy

作　　者：武海英 葛淑娴 李少琼 张玉 李肖华 高健[1] WU Haiying;GE Shuxian;LI Shaoqiong;ZHANG Yu;LI Xiaohua;GAO Jian(Department of Reproductive Genetics,Hebei General Hospital,Shijiazhuang,Hebei 050051,China)

机构地区：[1]河北省人民医院生殖遗传科,河北石家庄050051

出　　处：《中国优生与遗传杂志》2024年第2期360-364,共5页Chinese Journal of Birth Health & Heredity

摘　　要：目的 对一例GUCY2D基因复合杂合变异导致的罕见遗传病,Leber氏先天性黑蒙1型合并妊娠患者的突变基因进行分子检测及分析,并为该家系提供适当的遗传学咨询。方法 收集先证者及其配偶临床资料,应用全外显子组测序技术(WES)对两人外周血来源DNA进行分子遗传学检测,并用Sanger DNA测序技术对双方亲属进行验证分析,检测结果由专业的遗传学医师进行解读并为患者提供遗传学咨询。结果 患者本人及其丈夫患有严重视力障碍,患者表现为严重的视力障碍,色盲,夜间视力优于白天视力,但无眼球震颤,无儿童期刺激性“戳眼”,无中心视野缺损,无夜盲主诉,对患者查体未见皮肤及毛发色素沉着有特殊改变,神经查体未见异常,双眼视力无法测得。患者未接受任何相关干预性治疗。其丈夫患有白化病,对患者及其家系进行分子检测发现患者GUCY2D基因存在NM_000180.3:c.721G>C(p.Ala241Pro)和NM_000180.3:c.542G>A(p.Trp181^(*))两种变异的复合杂合状态,两种不同的变异分别来自患者父亲和母亲,两变异目前均为疑似致病变异,此复合杂合致病目前国内尚未报道。其丈夫为TYR基因NM_000372.4:c.832C>T(p.Arg278^(*))纯合致病,经家系分子检测和遗传学咨询,患者胎儿不存在患夫妻双方任何一方眼科疾病的风险,建议进行常规产检待产,一定程度上避免了非必要的侵入性诊断。结论 本研究确定了先证者及其配偶不同的致病突变,阐述了患者的致病原因,并为该患者提供了适宜的生育指导。Objective To molecularly test and analyze the mutated gene in a patient with Leber's congenital amaurosis type 1 combined with pregnancy,a rare genetic disorder caused by compound heterozygous variants in the GUCY2D gene,and to provide appropriate genetic counseling for the family line.Methods Clinical data of the proband and his spouse were collected.Whole exome sequencing(WES) was used to detect the molecular genetics of DNA derived from peripheral blood of the two patients,and Sanger DNA sequencing was used to verify the analysis of their relatives.Professional geneticists interpreted the test results and genetic counseling was provided to the patients.Results The patient and her husband suffered from severe visual impairment,and the patient presented with severe visual impairment,color blindness,better night vision than day vision,but no nystagmus,no irritating “poking eyes” in childhood,no central visual field defect,no complaints of night blindness,and no specific alterations in skin and hair pigmentation on examination,no abnormalities on neurological examination,no visual acuity in both eyes and no abnormalities on neurological examination.The patient's examination showed no specific changes in skin or hair pigmentation,neurological examination showed no abnormality and binocular visual acuity could not be measured.The patient did not receive any relevant interventional therapy.Her husband had albinism.Molecular testing of the patient and his family line revealed that the patient was compound heterozygous for NM_000180.3:c.721G>C(p.Ala241Pro)and NM_000180.3:c.542G>A(p.Trp181~*)in the GUCY2D gene,and the two different variants came from the patient's father and mother,and the two variants are Suspected PATHOGENIC VARIANT.This compound heterozygosity has not yet been reported in China.Her husband is TYR,NM_000372.4:c.832C>T(p.Arg278~*)purely pathogenic.After molecular testing of the family line and genetic counseling,the patient's fetus is not at risk for ophthalmologic disease in either spouse and rout

关 键 词：先天性黑蒙 GUCY2D 复合杂合致病 妊娠合并遗传病 遗传学咨询 

分 类 号：R714.25[医药卫生—妇产科学]