Clinical characterization of PLAG1- related Silver-Russell syndrome：A clinical report

Ping Dong; Nan Zhang; Ying Zhang; Chun-Xue Liu; Chun-Lan Li

doi:10.1016/j.ejmg.2023.104837

Clinical characterization of PLAG1- related Silver-Russell syndrome：A clinical report

Eur J Med Genet. 2023 Oct;66(10):104837. doi: 10.1016/j.ejmg.2023.104837. Epub 2023 Sep 4.

Authors

Ping Dong¹, Nan Zhang², Ying Zhang³, Chun-Xue Liu³, Chun-Lan Li⁴

Affiliations

¹ Department of Child Healthcare, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, PR China. Electronic address: dongping@fudan.edu.cn.
² Department of Child Healthcare, Northwest Women's and Children's Hospital, Xi'an, Shaanxi Province, PR China.
³ Department of Child Healthcare, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, PR China.
⁴ Department of Gyneocology, Children's Hospital of Anhui Province, Anhui Hospital of Children's Hospital of Fudan University, Hefei, Anhui Province, PR China. Electronic address: lcl13955777686@139.com.

PMID: 37673301
DOI: 10.1016/j.ejmg.2023.104837

Abstract

Background: Silver-Russell syndrome (SRS) is a rare genetic disorder that is mainly associated with prenatal and postnatal growth retardation. Loss of methylation on chromosome 11p15 and maternal uniparental disomy on chromosome 7 (upd(7)mat) are two common causes, accounting for approximately 50% and 10% of all patients, respectively. Pathogenic variants of genes, such as HMGA2, IGF2, CDKN1C, and PLAG1, have also been detected in patients with SRS. So far, SRS caused by PLAG1 alterations have only been described in two sporadic cases and three families.

Patient presentation: The genetic and clinical manifestations of SRS in a patient carrying a novel variant of PLAG1 were reported and these results were compared with those of five previously reported cases. Trio-based whole-exome sequencing revealed a heterozygous variation in PLAG1 (NM_002655.3: c.131del; p.(Asn44Thrfs*6)) in an infant girl with clinical suspicion of SRS. Familial studies confirmed that the mutation was inherited from her father. As seen in previously reported cases, the patient presented with prenatal and postnatal growth retardation, relative macrocephaly at birth, prominent forehead during infancy, and triangular face. However, no clinical characteristics such as feeding difficulties, hypothyroidism, or psychomotor and speech delay.

Conclusions: This study identified the sixth documented case of PLAG1 variants leading to SRS and expanded our knowledge of the molecular spectrum of SRS phenotypes.

Keywords: Clinical characterization; Mutation; PLAG1; Silver-Russell Syndrome.