1例常染色体隐性遗传脑-眼-颅面-生殖器畸形综合征致病性的遗传学分析  

Analysis of genetic variant in a patient with autosomal recessive cerebellar,ocular,craniofacial and genital syndrome(COFGS)

作　　者：刘庄[1] 王钦[1] 张琳 杨爱军[1] 李泽武 LIU Zhuang;WANG Qin;ZHANG Lin;YANG Aijun;LI Zewu(Department of Reproductive Medicine,Affiliated Hospital of Jining Medical University,Jining,Shandong 272029,China)

机构地区：[1]济宁医学院附属医院生殖医学科,山东济宁272029

出　　处：《中国优生与遗传杂志》2023年第7期1432-1435,共4页Chinese Journal of Birth Health & Heredity

基　　金：济宁市科技局重点研发项目(2022YXNS086);国家自然科学基金青年基金项目(81701526)。

摘　　要：目的探讨1例脑-眼-颅面-生殖器畸形综合征致病性家系的遗传学病因。方法通过高通量测序和Sanger测序的方法验证了先证者MAB21L1基因,并在其家系其他成员进行了Sanger验证。结果先证者及其妹妹MAB21L1基因均存在c.152G>A(p.Arg51Gln)的杂合变异。先证者母亲及其外祖母均携带该c.152G>A变异,先证者父亲不携带该变异。经多个数据库检索也没有相关基因突变的报道。根据美国医学遗传学与基因组学学会(ACMG)遗传变异标准与指南,MAB21L1基因的c.152G>A判定为致病性变异(PS3+PM1+PM2+PM5)。结论MAB21L1基因的c.152G>A变异可能是导致该家系患病的原因,该新发变异的报道丰富了MAB21L1基因的错义变异谱,也增加了MAB21L1基因在表型上以常染色体显性遗传模式的数量。Objective To investigate the genetic etiology of a family with cerebellar,ocular,craniofacial and genital malformation syndrome.Methods The MAB21L1 gene of the proband was assayed by high-throughput sequencing and Sanger sequencing,then Sanger sequencing of this gene was performed on other family members.Results One heterozygous c.152G>A(p.Arg51Gln)mutation was detected in MAB21L1of the proband and his sister.The proband’s mother and grandmother also have this c.152G>A mutation,however the proband’s father did not have the mutation.The c.152G>A mutation haven’t reported by multiple related databases.According to the American College of Medical Genetics and Genomics(ACMG)standards and guidelines for genetic variation,the c.152G>A mutation of MAB21L1was determined as a pathogenic variation(PS3+PM1+PM2+PM5).Conclusion The c.152G>A mutation of MAB21L1 would be the cause of this disease for this family.The report of this new mutation enriched the missense mutation spectrum of MAB21L1.It also increased the number of MAB21L1 disorders as autosomal dominant(AD)inheritance patterns.

关 键 词：脑-眼-颅面-生殖器畸形综合征(COFGS) MAB21L1基因 常染色体显性遗传 

分 类 号：R725.9[医药卫生—儿科]