一个中国汉族家系中存在一种新的11p13微缺失，该缺失包含PAX6基因，家系成员患有无虹膜、上睑下垂和智力发育迟缓。
A novel 11p13 microdeletion encompassing PAX6 in a Chinese Han family with aniridia, ptosis and mental retardation.
作者信息
Hu Ping, Meng Lulu, Ma Dingyuan, Qiao Fengchang, Wang Yan, Zhou Jing, Yi Long, Xu Zhengfeng
机构信息
State key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, 123# Tianfei Street, Baixia District Nanjing, 210029 China.
Department of Pathology, Nanjing University Medical School, Nanjing, China.
出版信息
Mol Cytogenet. 2015 Jan 22;8(1):3. doi: 10.1186/s13039-015-0110-2. eCollection 2015.
PURPOSE
To explore possible genetic aberrations in a Chinese family with aniridia, ptosis and mental retardation, and provide genetic evidence for the prenatal diagnosis.
METHODS
14 exons of PAX6 in the proband were sequenced by the Sanger sequencing technique. Multiplex ligation-dependent probe amplification (MLPA) technique was employed to further explore gene alterations of PAX6. Single nucleotide polymorphisms-array (SNP-array) assay was applied to screen potential pathologic genome-wide copy number variations (CNV).
RESULTS
There were no detectable pathogenic mutations in the 14 exons of PAX6 in the proband. MLPA indicated a heterozygous deletion encompassing all PAX6 gene regions covered and a partial upstream region. SNP-array assay detected a heterozygous 11p13 microdeletion with a length of 518 kb in the proband, spanning two whole annotated genes, elongation factor protein 4 (ELP4), the paired box gene 6 (PAX6), and partial IMP1 inner-mitochondrial membrane (IMMP1L) gene. SNP-array revealed her affected brother carried the identical deletion.
CONCLUSIONS
The 518 kb heterozygous deletion in 11p13 encompassing PAX6 should be the genetic etiology for the familial aniridia.
目的
探究一个患有无虹膜、上睑下垂和智力发育迟缓的中国家系中可能存在的基因畸变情况，为产前诊断提供遗传学依据。
方法
采用桑格测序技术对先证者的PAX6基因的14个外显子进行测序。运用多重连接依赖探针扩增（MLPA）技术进一步探究PAX6基因的改变情况。应用单核苷酸多态性阵列（SNP-阵列）分析筛选潜在的全基因组病理性拷贝数变异（CNV）。
结果
先证者的PAX6基因的14个外显子中未检测到致病性突变。MLPA显示存在一个杂合性缺失，涵盖所有PAX6基因区域及部分上游区域。SNP-阵列分析检测到先证者存在一个长度为518 kb的11p13杂合性微缺失，跨越两个完整注释基因，即延伸因子蛋白4（ELP4）、配对盒基因6（PAX6）以及部分线粒体内膜蛋白1（IMMP1L）基因。SNP-阵列显示其患病的兄弟携带相同的缺失。
结论
11p13区域包含PAX6的518 kb杂合性缺失应为该家族性无虹膜的遗传病因。
Zotero 插件