| Summary: | 碩士 === 臺灣大學 === 分子醫學研究所 === 98 === Objective: Silver-Russell syndrome (SRS) is a clinical and genetically heterogenous disorder characterized by severe intrauterine growth restriction, postnatal growth retardation, and specific dysmorphisms. But no consensus on clinical diagnostic criteria was made. Maternal uniparental
disomy of chromosome 7 and hypomethylation of the imprinting in 11p15 are the major epigenetic disturbance in patients of Silver-Russell syndrome. The incidence of epigenetic disturbance in Taiwanese patients of Silver-Russell syndrome and the epigenetic-phenotype analysis have never been surveyed.
Materials and methods: We report on our experience of molecular testing in 107 Taiwanese patients referred for routine diagnostics of Silver-Russell syndrome. We also retrospectively investigated the clinical manifestations of those probands with suspected Silver-Russell syndrome phenotypes. We designed a clinical SRS scoring system to help the pediatrians in clinical setting .
Results: The molecular results in our study cohort showed that maternal uniparental disomy of chromosome 7 and hypomethylation of the H19 imprinted region in 11p15 accounts for the epigenetic disturbance in 3.6% and 26.8% of patients with clinically scored as SRS group (n=56).
respectively. All cases with epimutation were scored >= 6 by the clinical SRS scoring system. Maternal uniparental disomy of chromosome 7 carriers showed relatively mild Silver-Russell syndrome phenotype as compared with 11p15 epimutation carrier. The percentage of small for gestational age, postnatal growth retardation, typical facies, aymmetry and clinodactyly of 5th fingers was significantly different between SRS group and SRS-like group.
Conclusions:The detection rate of epigenetic anomalies in our study cohort of 56 Taiwanese individuals with
SRS phenotypes was around 30.4 %; epimutations at the PEG1/MEST locus and the H19/IGF2 locus occurred in about 3.6% and 26.8% of patients with SRS respectively. By our new clinical SRS scoring system, we can quantify the phenotype severity, and it showed that “clinical SRS score 6” was a good discrimination point to distinguish the cases with or without epimutation for SRS inour study.
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