Sun Mei, Li Qing, Zhang Ying, Cai Yingzi, Dong Yan, Shu Jianbo, Li Dong, Cai Chunquan
Graduate College of Tianjin Medical University, Tianjin Medical University, Tianjin, Peoples' Republic of China.
Tianjin Children's Hospital (Children's Hospital of Tianjin University), Tianjin, Peoples' Republic of China.
Glob Med Genet. 2024 Jan 16;11(1):13-19. doi: 10.1055/s-0043-1778089. eCollection 2024 Jan.
Variants of ubiquitin-specific protease 7 ( ) gene in humans are associated with a neurodevelopmental disorder-Hao-Fountain syndrome, its core symptoms including developmental delay, intellectual disability, and speech delay. Other variable symptoms can affect multiple systems. In present study, we report two patients with core features from two unrelated consanguineous families originating from the Tianjin Children's Hospital. Genomic DNA was extracted from the peripheral blood samples collected from the probands with their family members and whole-exome sequencing (WES) was used to detect the pathogenic genes in the probands. Suspected variants were subsequently validated by Sanger sequencing. In family 1, WES revealed that the proband carried the de novo variant c.2697A > C (p.Leu899Phe) in (NM_003470.3). In family 2, WES identified the variant c.3305A > C (p.Asn1102Thr) in (NM_003470.3) from the proband. We reported two cases of Hao-Fountain syndrome caused by novel variants. In addition, we report the first case of mosaicism with a variant in Chinese family. Our findings demonstrate the importance of WES in diagnosis of genetic diseases and expands the variants spectrum in Hao-Fountain syndrome. Moreover, we summarize the cases caused by variants in the literature. Our study can provide a vital reference for the diagnosis of future cases.
泛素特异性蛋白酶7（ ）基因的变异与一种神经发育障碍——郝-方丹综合征有关，其核心症状包括发育迟缓、智力残疾和语言发育迟缓。其他可变症状可影响多个系统。在本研究中，我们报告了两名来自天津儿童医院的两个无关近亲家庭的具有核心特征的患者。 从先证者及其家庭成员采集的外周血样本中提取基因组DNA，并使用全外显子组测序（WES）检测先证者中的致病基因。随后通过桑格测序验证疑似变异。在家庭1中，WES显示先证者携带 （NM_003470.3）基因的新生变异c.2697A＞C（p.Leu899Phe）。在家庭2中，WES在先证者中鉴定出 （NM_003470.3）基因的变异c.3305A＞C（p.Asn1102Thr）。 我们报告了两例由新的 变异引起的郝-方丹综合征病例。此外，我们报告了中国家庭中首例具有 变异的嵌合体病例。我们的研究结果证明了WES在遗传疾病诊断中的重要性，并扩展了郝-方丹综合征的 变异谱。此外，我们总结了文献中由 变异引起的病例。我们的研究可为未来病例的诊断提供重要参考。
