眼皮肤白化病合并天使综合征基因诊断及临床表型分析  

Genetic diagnosis and clinical phenotype analysis of ocular albinism combined with Angelman syndrome

作　　者：马佳 王琳 王钱 强荣 彭飞 Ma Jia;Wang Lin;Wang Qian;Qiang Rong;Peng Fei(Center of Medical Genetics,Northwest Women’s and Children’s Hospital,Xi’an 710061,China;Blood Transfusion Department,Northwest Women’s and Children’s Hospital,Xi’an 710061,China;General Surgery Department,Northwest Women’s and Children’s Hospital,Xi’an 710061,China)

机构地区：[1]西北妇女儿童医院医学遗传中心,西安710061 [2]西北妇女儿童医院输血科,西安710061 [3]西北妇女儿童医院普通外科,西安710061

出　　处：《国际遗传学杂志》2024年第5期399-405,共7页International Journal of Genetics

基　　金：陕西省重点研发计划项目(2023-YBSF-305)。

摘　　要：目的通过分析眼皮肤白化病(oculocutaneous albinism,OCA)合并天使综合征(Angelman syndrome,AS)的家系病例,明确其分子致病病因,总结OCA合并AS的临床表型谱。方法应用全外显子测序、CNV检测、Sanger测序和荧光定量PCR技术,对核心家庭成员进行变异分析,寻找分子致病病因。结果患儿遗传了来自父源的OCA2基因c.2359G>A杂合变异,并合并新发的染色体15q11.2-q13.1区段6.58 Mb的杂合缺失,导致了患儿眼皮肤白化病合并天使综合征的临床表型。结论在AS片段缺失合并OCA2基因错义变异影响的患者中,存在明显的基因型-表型叠加现象。该研究丰富了白化病合并AS的表型谱,为临床诊断和和遗传咨询提供了有价值的参考依据。Objective This study aims to elucidate the molecular pathogenic causes and summarize the clinical phenotypic spectrum of a combined presentation of oculocutaneous albinism(OCA)and Angelman syndrome(AS)through the analysis of a family case.Methods To identify the molecular pathogenic causes,variations in the core family members were investigated using whole-exome sequencing,copy number variation analysis,Sanger sequencing,and quantitative fluorescent PCR techniques.Results The affected child inherited a heterozygous c.2359G>A variant in the OCA2 gene from the paternal and carried a de novo heterozygous deletion of 6.58 Mb in the q11.2-q13.1 region of chromosome 15.These genetic alterations manifested in the clinical phenotypes of oculocutaneous albinism combined with Angelman syndrome.Conclusion The findings reveal a significant genotype-phenotype correlation in patients with AS segment deletions combined with OCA2 gene missense mutant.This study broadens the phenotypic spectrum of albinism associated with AS,offering valuable insights for clinical diagnosis and genetic counseling.

关 键 词：眼皮肤白化病 天使综合征 变异 片段缺失 全外显子测序 

分 类 号：R725.9[医药卫生—儿科]