ESPE Abstracts

Background: Nearly half of SRS epigenetic etiology is unknown. Effect of GH in SRS is not exact.

Objective: To determine novel gene or imprinted gene associated with pathogenicity of Silver–Russell syndrome (SRS) through detection genome-wide methylation differences. To observe GH efficacy in SRS and the relationship between GH and epigenetic changes.

Method: To detect genome-wide methylation site through the Illumina 450K methylation chip in seven SRS and five controls matched age. Other ten cases of SRS were analyzed GH efficacy.

Results: Imprinted gene OSBPL5 has the most significant methylation difference site in case group and normal control group (P=0.023, β=−0.243). And the gene is located on 11p15–45 UTR, it is quite possible pathogenic. Five important genes were found might related with SRS: TGFβ3, GAP43, HSF1, NOTCH4, and MYH14. Ten SRS with GH treatment, the average follow-up period was 13.2 months. The average GH dosages was 0.15 IU/kg per day. Growth velocity (GV) was 9.53+3.918 cm/year. which was higher than normal children’s GV (5 cm/year), P=0.005. Five out of ten cases did epigenetic detection. One patient was matUPD (7) positive and his GV was 11.13 cm/year. Two patients were 11p15 ICR1 hypomethylation and their GV were 8 and 9.141 cm/year respectively. The other two cases were not found in epigenetic changes, whose GV were 14.4 and 9.54 cm/year.

Conclusion: The imprinted gene OSBPL5 is quite possible pathogenicity of SRS. Other five important genes: TGFβ3, HSF1, GAP43, NOTCH4, and MYH14 may be related to SRS. This group of SRS have good GH efficacy. One case of UPD (7) mat was higher GV than two patients who were 11p15 ICR1 hypomethylation.

Funding: This work was supported by the Basic-Clinical Research Fund of Capital Medical University (grant number 14JL75).