Prof Yulin Chen

Abstract:

Background

Primary hypertrophic osteoarthropathy (PHO) is a genetically and clinically heterogeneous systematic disorder caused by mutations in genes HPGD and SLCO2A1. The purpose of the present study is to provide useful information for the early and precise diagnosis of PHO and identify causative mutations in Chinese PHO children.

Methods and results

The clinical manifestations, radiographic features of seven Chinese pediatric patients were systematically analyzed. Targeted exome sequencing identified a previously reported c.310_311delCT mutation and a novel common splicing site mutation c.324 + 5G > A in the HPGD gene. Relative quantitative real time PCR validated a novel deletion of the exon 4 in the same gene. Neither mutations nor structural variations in the gene SLCO2A1 were detected.

Conclusions

In the present study, homozygous or compound heterozygous HPGD mutations were identified in seven Chinese pediatric patients, suggesting an autosomal recessive inheritance. The c.310_311delCT mutation and the splicing site mutation c.324 + 5G > A were likely to be mutational hotspots in Chinese PHO patients. For the first time, a structural variation of the HPGD gene was reported. Homozygous, compound heterozygous mutations or structural variation identified in the HPGD gene proposed that targeted exome sequencing may be a preferable method for pediatric PHO diagnosis and mutation analysis.