Focal facial dermal dysplasias type III: Two families with Setleis syndrome in China
Focal facial dermal dysplasias type III: Two families with Setleis syndrome in China
复制标题
局灶性面部真皮发育不良Ⅲ型：中国两个Setleis综合征家系
DOI：
10.1111/1346-8138.16488
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发表时间：
2022-06-17
影响因子：
3.1
通讯作者：
Li, Ming
中科院分区：
文献类型：
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作者：
Cao, Qiaoyu;Zhang, Shuai;Li, Ming
局灶性面部真皮发育不良 III 型 (FFDD III)，俗称 Setleis 综合征（SS；Online Mendelian Inheritance in Man #227260），是一种局灶性面部真皮发育不良，其特征是双颞部萎缩性皮肤病变。据报道，TWIST2 基因的纯合突变和染色体 1p36.22p36.21 的拷贝数变异 (CNV) 是其致病机制。在这项研究中，我们收集了一个受 FFDD 影响的中国大家庭的 DNA 样本，没有发现 TWSIT2 突变。为了确定潜在的遗传原因，我们对家族 1 进行了多点参数连锁分析和单倍型分析，并将 SS 映射到 Chr1:14.074-20.524cM 区域（rs2401090-rs2294642）。通过Sanger测序鉴定拷贝数变异，断点为Chr1：11695972和Chr1：11829858。该区域包含 8 个基因，包括 FBXO2、FBXO44、FBXO6、MAD2L2、DRAXIN、AK125437、AGTRAP 和 C1orf167。 SS第二个家系没有候选基因突变。我们的研究进一步缩小了导致 SS 的 CNV 大小 (Chr1:11696993-11829858)，并重点关注八个基因。
Focal facial dermal dysplasias type III (FFDD III), commonly known as Setleis syndrome (SS; Online Mendelian Inheritance in Man #227260), is a type of focal facial dermal dysplasia, characterized by bitemporal atrophic skin lesion. The homozygous mutations in the TWIST2 gene and copy number variants (CNV) at chromosome 1p36.22p36.21 were reported as the pathogenic mechanism. In this study, we collected DNA samples from a large Chinese family affected by FFDD and found no mutation of TWSIT2. To determine the underlying genetic cause, we performed a multipoint parameter linkage analysis and haplotype analysis of the family 1 and mapped SS to a region Chr1:14.074-20.524cM (rs2401090-rs2294642). Copy number variant was identified by Sanger sequencing, which breakpoints were Chr1:11695972 and Chr1:11829858. The region contains eight genes, including FBXO2, FBXO44, FBXO6, MAD2L2, DRAXIN, AK125437, AGTRAP, and C1orf167. There were no candidate gene mutations of the second family with SS. Our study further reduced the size of CNV resulting in SS (Chr1:11696993-11829858) and focused on eight genes.