Genetics and Prenatal Diagnosis Center, The Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Jianshe Rd, Erqi District, Zhengzhou, Henan, 450052, China; The Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, China.
Genetics and Prenatal Diagnosis Center, The Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Jianshe Rd, Erqi District, Zhengzhou, Henan, 450052, China.
Eur J Med Genet. 2022 Apr;65(4):104454. doi: 10.1016/j.ejmg.2022.104454. Epub 2022 Feb 16.
This ASXL2 gene encodes a member of a family of epigenetic regulators that bind various histone-modifying enzymes and are involved in the assembly of transcription factors at specific genomic loci. Recent research has found that pathogenic variants in ASXL2 gene can lead to Shashi-Pena syndrome. However, clinical reports of individuals with damaging ASXL2 variants were limited and clinical phenotypic information may also be incomplete at present. Here, we reported a patient from Chinese family presenting with Shashi-Pena syndrome duo to a nonsense variant c.2485C > T; p. (Gln829*) in ASXL2 and analyzed the clinical phenotypes of the patient. In addition to the typical facial appearance, feeding difficulty, cardiac dysfunction and developmental delay, the patient also demonstrated multiple clinical problems not reported in other published cases, including granulocytopenia, thrombocytopenia and "single transverse palmar crease". Additionally, this is also the first case of premature death associated to Shashi-Pena syndrome induced by ASXL2 variants in a Chinese population. Our results provided important information for genetic counseling of the family and broaden the spectrum of phenotypes and genetic variations of the syndrome.
该 ASXL2 基因编码表观遗传调控因子家族的成员，该家族结合各种组蛋白修饰酶，并参与特定基因组位置转录因子的组装。最近的研究发现，ASXL2 基因突变可导致 Shashi-Pena 综合征。然而，目前临床上关于具有破坏性 ASXL2 变异个体的报道有限，且临床表型信息也可能不完全。在这里，我们报道了一个来自中国家庭的患者，该患者由于 ASXL2 中的无义变异 c.2485C>T；p.（Gln829*）而患有 Shashi-Pena 综合征，并分析了患者的临床表型。除了典型的面部特征、喂养困难、心脏功能障碍和发育迟缓外，该患者还表现出其他已发表病例中未报道的多种临床问题，包括粒细胞减少症、血小板减少症和“单一横向掌褶”。此外，这也是首例由中国人群 ASXL2 变异引起的 Shashi-Pena 综合征相关的过早死亡病例。我们的结果为该家系的遗传咨询提供了重要信息，并拓宽了该综合征的表型和遗传变异谱。
