医学外显子测序对眼皮肤白化病2型的诊断及遗传分析  

Molecular diagnosis and genetic analysis of Oculocutaneous Albinism Type 2 by using medical exome sequencing platform

作　　者：刘渊[1] 黄菊[2] 谢素贞[3] 王兴旺 李发科 丁红珂[1] 曾玉坤[1] Liu Yuan;Huang Ju;Xie Suzhen;Wang Xingwang;Li Fake;Ding Hongke;Zeng Yukun(Medical Genetics Center,Guangdong Women and Children Hospital,Guangzhou,Guan gdong 511442,China;Department of Reproductive Health and Infertility,Guangdong Women and Children Hospital,Guangzhou,Guangdong 511442,China;Department of ophthalmology,Giangdong Women and Children Hospital,Guangzhou,Guangdong 511442,China)

机构地区：[1]广东省妇幼保健院医学遗传中心,广东广州511442 [2]广东省妇幼保健院生殖健康与不孕症科,广东广州511442 [3]广东省妇幼保健院眼科,广东广州511442

出　　处：《中国产前诊断杂志（电子版）》2022年第4期11-17,共7页Chinese Journal of Prenatal Diagnosis(Electronic Version)

基　　金：广东省医学科研基金项目(A2020065)。

摘　　要：目的利用医学外显子测序技术对眼皮肤白化病(oculocutaneous albinism,OCA)2型进行诊断及家系遗传分析,为先证者家庭提供遗传学病因诊断和再生育风险评估。方法2021年因不孕症来广东省妇幼保健院就诊的一对夫妇,经体外试管婴儿辅助生殖技术后出生疑似白化病患儿,患儿家庭寻求病因及再生育风险咨询。本研究以此家系为研究对象,利用家系医学外显子测序技术对先证者及其父母进行检测及Sanger测序验证,通过生物信息学分析、数据库查询及位点分析,找到可能致病的基因变异,并对变异位点进行遗传模式分析。结果医学外显子检测及Sanger测序验证,发现该先证者的OCA2(NM_000275.3)基因存在两个表型相关变异且构成复合杂合变异;其中,位点c.632C>T(p.P211L)遗传自母亲,位点c.535A>G(p.K179E)遗传自父亲,符合OCA2型的遗传模式,经数据查询和变异分类评级,此两个变异均为可能致病变异位点。结论本研究采用医学外显子测序成功对1例OCA2型患者进行了分子诊断,该患者携带两个遗传自父母可能致病变异,构成复合杂合变异。本研究结果为该先证者的致病原因和其父母再次生育提供了可靠的分子诊断和遗传咨询。同时,本案例中一个变异位点c.535A>G(p.K179E)目前相关报道病例不多,本研究为该变异提供了新的临床证据支持。Objective To detect the pathogenic variants in OCA2 gene in a family with albinism by using medical exome sequencing technology,and provide genetic counselingfor the family according to the result.Methods In 2021,a couple with infertility was referred to our hospital for IVF treatment.After several cycles of IVF therapy,a boy with suspected albinism was born.Study was designed to find the cause of albinism for the family.By using trio-exome sequencing technology,we found 2 variants in OCA2 gene in the proband.Sanger sequencing validations for the two variants of OCA2 were performed basing on the DNA of the proband and his parents.Inheritance pattern was also analyzed after the validation experiments.Results Two phenotype-related compound heterozgous variants were found in OCA2(NM_000275.3)gene in the proband,after medical exome sequencing and Sanger sequencing validations.Those two variants c.632C>T(p.P211Lc)and c.535A>G(p.K179E),were inherited from his mother and father,respectively.By searching the current database and variant classification,both of those two variants were determined as a likely pathogenic variants.Conclusion By using medical exome sequencing technology,we successfully detected two likely-pathogenic variants in a proband with OCA type 2.This combination of compound heterozygous variants were inherited from his parents.In this study,a reliable molecular diagnosis and genetic counseling were provided for both the proband and the next pregnancy of his family.Meanwhile,this case supplement the insufficient clinic literature for the rare variant of OCA2 gene c.535A>G(p.K179E).

关 键 词：白化病 OCA2基因 医学外显子测序 遗传咨询 

分 类 号：R715.5[医药卫生—妇产科学]