Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
Oral Dis. 2018 Oct;24(7):1247-1254. doi: 10.1111/odi.12894. Epub 2018 Jun 11.
Rieger syndrome (RS) is a genetic disorder characterized by abnormal development of the eyes, teeth, and umbilicus, and the paired-like homeodomain 2 (PITX2) gene is often implicated in its pathogenesis. This study aimed to identify the underlying genetic defect in a Chinese patient with RS.
DNA samples were screened for PITX2 gene mutations and copy number variations (CNVs) using Sanger sequencing and genomic quantitative PCR analysis (qPCR). Chromosomal microarray analysis (CMA) was performed to fine-map the CNVs.
The proband suffered from severe hypodontia and conical teeth in her permanent dentition. No PITX2 point mutations were found in this Chinese family, but a heterozygous deletion involving PITX2 was suspected and verified by the SNPs analysis and qPCR in the proband. An approximately 0.47 Mb (chr4: 111, 334, 313-111, 799, 327, GRCh37/hg19) deletion including PITX2 was finally determined by CMA.
To our knowledge, this is the first reported case of RS caused by a CNV of the PITX2 gene in a Chinese patient. CNV screening must be considered if point mutation screens yield negative results in these patients. The distribution of SNP genotypes among family members may also provide clues about gene deletion.
Rieger 综合征（RS）是一种遗传性疾病，其特征为眼睛、牙齿和脐部发育异常，而配对样同源结构域 2（PITX2）基因常与该病的发病机制有关。本研究旨在鉴定一位 RS 中国患者的潜在遗传缺陷。
采用 Sanger 测序和基因组定量 PCR 分析（qPCR）对 PITX2 基因突变和拷贝数变异（CNV）进行 DNA 样本筛选。采用染色体微阵列分析（CMA）对 CNV 进行精细定位。
先证者恒牙列存在严重的先天性缺牙和锥形牙。该中国家系中未发现 PITX2 点突变，但 SNP 分析和先证者 qPCR 提示存在 PITX2 杂合性缺失。CMA 最终确定了包含 PITX2 的约 0.47Mb（chr4：111,334,313-111,799,327,GRCh37/hg19）缺失。
据我们所知，这是首例报道的由中国患者 PITX2 基因突变引起的 RS 病例。如果这些患者的点突变筛查结果为阴性，必须考虑 CNV 筛查。家系成员 SNP 基因型的分布也可能为基因缺失提供线索。
