Investigation of Mutations in H19, IGF2, CDKN1C, KCNQ1, and NSD1 Genes in Iranian Children Suspected of Silver-Russell Syndrome (SRS) and Beckwith-Wiedemann Syndrome (BWS) with MS-MLPA

Background: Silver-Russell Syndrome (SRS) and Beckwith-Wiedemann Syndrome (BWS) are two syndromes that are poorly diagnosed in many affected people due to mild and subtle symptoms, genetic complexity, and lack of familiarity with the hallmarks. Objective: The present study was conducted with the aim of determining mutations in H19, IGF2, CDKN1C, KCNQ1, and NSD1 genes in Iranian children suspected of SRS and BWS by the MS-MLPA method. Methods: In this case series study, which was conducted in 2022 in Pars Genome Laboratory, Karaj, Iran, 10 children suspected of SRS or BWS syndrome were included. These 10 Iranian children were referred by pediatric endocrinologists. 5 ml of peripheral blood was taken per patient for DNA extraction. MS-MLPA method was undertaken for possible mutations (methylation and deletion) in H19, IGF2, CDKN1C, KCNQ1, and NSD1 genes. Results: The interpretation of MS-MLPA results showed that out of 10 children (4 boys and 6 girls) suspected of having SRS or BWS syndrome (based on the pediatric endocrinologist’s diagnosis), only 3 children were definitively diagnosed with SRS or BWS syndrome. Based on this, methylation changes in the promoter of ICR1 and ICR2, which are related to the genes H19, IGF2, CDKN1C, KCNQ1, and NSD1, lead to the development of SRS or BWS syndrome. Conclusion: The present findings showed that methylation changes in H19, IGF2, CDKN1C, KCNQ1, and NSD1 genes are associated with the occurrence of SRS or BWS syndrome. In this study, we show that MS-MLPA can serve as a rapid, inexpensive, and reliable method for the molecular diagnosis of these syndromes.