Dong Ping, Zhang Nan, Zhang Ying, Liu Chun-Xue, Li Chun-Lan
Department of Child Healthcare, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, PR China.
Department of Child Healthcare, Northwest Women's and Children's Hospital, Xi'an, Shaanxi Province, PR China.
Eur J Med Genet. 2023 Oct;66(10):104837. doi: 10.1016/j.ejmg.2023.104837. Epub 2023 Sep 4.
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.
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.
This study identified the sixth documented case of PLAG1 variants leading to SRS and expanded our knowledge of the molecular spectrum of SRS phenotypes.
Silver-Russell综合征（SRS）是一种罕见的遗传性疾病，主要与产前和产后生长发育迟缓有关。11号染色体p15区域甲基化缺失和7号染色体母源单亲二倍体（upd(7)mat）是两个常见病因，分别占所有患者的约50%和10%。在SRS患者中也检测到了HMGA2、IGF2、CDKN1C和PLAG1等基因的致病变异。到目前为止，由PLAG1改变引起的SRS仅在两例散发病例和三个家族中被描述过。
报告了一名携带PLAG1新变异的SRS患者的遗传和临床表现，并将这些结果与之前报告的五例病例进行了比较。基于三联体的全外显子组测序在一名临床怀疑患有SRS的女婴中发现了PLAG1基因的杂合变异（NM_002655.3: c.131del; p.(Asn44Thrfs*6)）。家族研究证实该突变遗传自她的父亲。与之前报告的病例一样，该患者表现出产前和产后生长发育迟缓、出生时相对头大、婴儿期前额突出和三角形脸。然而，没有出现喂养困难、甲状腺功能减退或精神运动和语言发育迟缓等临床特征。
本研究确定了第六例记录在案的由PLAG1变异导致SRS的病例，并扩展了我们对SRS表型分子谱的认识。
