A novel 4q25 microdeletion encompassing PITX2 associated with Rieger syndrome

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.