Epigenotype, genotype, and phenotype analysis of taiwanese patients with silver–russell syndrome

Hsiang Yu Lin, Chung Lin Lee, Sisca Fran, Ru Yi Tu, Ya Hui Chang, Dau Ming Niu, Chia Ying Chang, Pao Chin Chiu, Yen Yin Chou, Hui Pin Hsiao, Meng Che Tsai, Mei Chyn Chao, Li Ping Tsai, Chia Feng Yang, Pen Hua Su, Yu Wen Pan, Chen Hao Lee, Tzu Hung Chu, Chih Kuang Chuang, Shuan Pei Lin

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)


Background: Silver–Russell syndrome (SRS) is a clinically and genetically heterogeneous disorder characterized by severe intrauterine growth retardation, poor postnatal growth, characteristic facial features, and body asymmetry. Hypomethylation of the imprinted genes of the chromosome 11p15.5 imprinting gene cluster and maternal uniparental disomy of chromosome 7 (mUPD7) are the major epigenetic disturbances. The aim of this study was to characterize the epigenotype, geno-type, and phenotype of these patients in Taiwan. Methods: Two hundred and six subjects with clinically suspected SRS were referred for diagnostic testing, which was performed by profiling the methylation of H19-associated imprinting center (IC) 1 and the imprinted PEG1/MEST region using methylation-specific multiplex ligation-dependent probe amplification and high-resolution melting analysis with a methylation-specific polymerase chain reaction assay. We also applied a whole genome strategy to detect copy number changes and loss of heterozygosity. Clinical manifestations were recorded and analyzed according to the SRS scoring system proposed by Bartholdi et al. Results: Among the 206 referred subjects, 100 were classified as having a clinical diagnosis of SRS (score ≥ 8, maximum = 15) and 106 had an SRS score ≤ 7. Molecular lesions were detected in 45% (45/100) of the subjects with a clinical diagnosis of SRS, compared to 5% (5/106) of those with an SRS score ≤ 7. Thirty-seven subjects had IC1 hypomethylation, ten subjects had mUPD7, and three subjects had microdeletions. Several clinical features were found to be statistically different (p < 0.05) between the “IC1 hypomethylation” and “mUPD7” groups, including relative macrocephaly at birth (89% vs. 50%), triangular shaped face (89% vs. 50%), clinodactyly of the fifth finger (68% vs. 20%), and SRS score (11.4 ± 2.2 vs. 8.3 ± 2.5). Conclusions: The SRS score was positively correlated with the molecular diagnosis rate (p < 0.001). The SRS subjects with mUPD7 seemed to have fewer typical features and lower SRS scores than those with IC1 hypomethylation. Careful clinical observation and timely molecular confirmation are important to allow for an early diagnosis and multidisciplinary management of these patients.

期刊Journal of Personalized Medicine
出版狀態Published - 2021 11月

All Science Journal Classification (ASJC) codes

  • 醫藥(雜項)


深入研究「Epigenotype, genotype, and phenotype analysis of taiwanese patients with silver–russell syndrome」主題。共同形成了獨特的指紋。