Case Report ARTICLE
Rare de novo IGF2 variant on the paternal allele in a patient with Silver-Russell syndrome
- 1Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, China
- 2Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, China
- 3Other, China
- 4Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, China
- 5Other, China
- 6State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, China
- 7Department of Pediatrics, The First Hospital of China Medical University, China
- 8Jinjiang Maternal and Child Health Hospital, China
- 9Department of Pediatric Pulmonology, Shengjing Hospital of China Medical University, China
Silver-Russell syndrome (SRS) is a rare, well-recognized disorder characterized by growth restriction, including intrauterine and postnatal growth. Most SRS cases are caused by hypomethylation of the paternal imprinting center 1 (IC1) in chromosome 11p15.5 and maternal uniparental disomy in chromosome 7 (UPD7). Here, we report on a Chinese family with a 4 year old male proband presenting with low birth weight, growth retardation, short stature, a narrow chin, delayed bone age, and speech delays, as a result of a rare molecular etiology. Whole-exome sequencing was conducted, and a novel de novo IGF2 splicing variant, NM_000612.4: c.157+5G>A, was identified on the paternal allele. In vivo functional analysis by RT-PCR and Sanger sequencing revealed that the variant leads to an aberrant RNA transcript lacking exon 2. Our results further confirm the IGF2 variant mediates SRS and expand the pathogenic variant and phenotypic spectrum of IGF2-mediated SRS. The results indicate that, beyond DNA methylation and UPD7 and CDKN1C variant tests, IGF2 gene screening should also be considered for SRS molecular diagnoses.
Keywords: IGF2,, de novo, Splicing variant, Silver-Russell Syndrome, Whole-exome-sequencing
Received: 05 Jul 2019;
Accepted: 23 Oct 2019.
Copyright: © 2019 Xia, Lyu, Li, Li, Zhang, Yin, Mao, Li, Kong, Liang, Jiang, Li-Ling, Liu and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Jun Wei, Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Benxi, Liaoning, China, JunWei003@126.com