PHF21A(PHD指蛋白21A)基因,位于11号染色体的短臂中,编码BHC80,这是赖氨酸特异性去甲基酶1的组成部分,REST(LSD1-CoREST)复合物的辅阻遏物。BHC80主要在人胎儿脑和骨骼肌中表达,并在胚胎发生过程中充当几种神经元基因的调节剂。来自文献的数据涉及PHF21A变体与Potocki-Shaffer综合征(PSS),由PHF21A单倍体不足引起的连续基因缺失障碍,ALX4和EXT2基因。PSS综合征的临床主要特征是多发性外生骨(由于EXT2受累),双顶孔(由于ALX4的参与),智力残疾,和颅面异常(由于PHF21A受累)。迄今为止,据我们所知,PHF21A相关疾病临床表型的详细描述在文献中没有描述;事实上,仅报道了14例具有仅涉及PHF21A基因的微缺失移码或无义变体的受试者。所有报告病例均未出现ALX4或EXT2变异,其临床特征与PSS诊断不符。在这里,通过使用外显子组测序,和感兴趣区域的桑格测序,我们描述了一例具有父系遗传(5%的镶嵌性)的PHF21A基因(c.649_650del;p.Gln217ValfsTer6)截断变体的儿童,讨论新的证据.总之,这些患者表现出不同的临床表现,主要包括智力残疾,癫痫,低张力,和畸形特征。我们的研究有助于描述PHF21A相关疾病患者的基因型-表型谱;然而,文献中有限的数据无法为PHF21A相关疾病患者提供精确的诊断方案.
PHF21A (PHD finger protein 21A) gene, located in the short arm of chromosome 11, encodes for BHC80, a component of the Lysine Specific Demethylase 1, Corepressor of REST (LSD1-CoREST) complex. BHC80 is mainly expressed in the human fetal brain and skeletal muscle and acts as a modulator of several neuronal genes during embryogenesis. Data from literature relates PHF21A variants with Potocki-Shaffer Syndrome (PSS), a contiguous gene deletion disorder caused by the haploinsufficiency of PHF21A, ALX4, and EXT2 genes. Clinical cardinal features of PSS syndrome are multiple exostoses (due to the EXT2 involvement), biparietal foramina (due to the ALX4 involvement), intellectual disability, and craniofacial anomalies (due to the PHF21A involvement). To date, to the best of our knowledge, a detailed description of PHF21A-related disorder clinical phenotype is not described in the literature; in fact, only 14 subjects with microdeletion frameshift or nonsense variants concerning only PHF21A gene have been reported. All reported cases did not present ALX4 or EXT2 variants, and their clinical features did not fit with PSS diagnosis. Herein, by using Exome sequencing, and Sanger sequencing of the region of interest, we describe a
case of a child with a paternally inherited (mosaicism of 5%) truncating variant of the PHF21A gene (c.649_650del; p.Gln217ValfsTer6), and discuss the new evidence. In conclusion, these patients showed varied clinical expressions, mainly including the presence of intellectual disability, epilepsy, hypotonia, and dysmorphic features. Our study contributes to describing the genotype-phenotype spectrum of patients with PHF21A-related disorder; however, the limited data in the literature have been unable to provide a precise diagnostic protocol for patients with PHF21A-related disorder.