[亨特综合征血统患者的临床表型、遗传特征和永生细胞系的建立]。

Benchang Li, Fengyu Che, Lidangzhi Mo, Liyu Zhang, Guoxia Wang, Ying Yang
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引用次数: 0

摘要

目的探讨中国亨特综合征患者的临床表型和遗传变异,并为患者建立永生细胞系:方法:选取2022年7月在西安市儿童医院就诊的6名患者作为研究对象。收集临床数据。对血统成员进行全外显子测序。通过桑格测序验证了候选变异。此外,用 Epstein-Barr 病毒转染外周 B 淋巴细胞,以创建永生化细胞系,然后对其进行酶活性分析:患者是一名五岁七个月大的男孩,四肢僵硬,关节肿大。结果:患者是一名五岁零七个月大的男孩,表现为四肢僵硬、关节肿大,3 个月大时就出现疝气、头胛畸形和桶状胸。他的叔叔也有四肢僵硬、听力差、失明和右腹股沟斜疝等症状。以上特征与亨特综合征相似。基因检测发现,孩子和他的叔叔都携带有一个 IDS(NM_000202.8):c.823G>A(p.D275N)变异,而这一变异此前从未报道过。生物信息学分析表明,D275是一个高度保守的位点,D275N变异可能会影响蛋白质空间构象的稳定性,从而降低酶的催化活性。为孩子及其父母成功构建的永生化淋巴母细胞系表现出体积增大、形状不规则、毛刺结构和集群生长。而患者永生化淋巴母细胞的 IDS 活性值低于检测限。根据美国医学遗传学和基因组学学院(ACMG)的指南,该变异被归类为可能致病(PS3+PM2_支持+PM5+PP1+PP3):上述发现丰富了亨特综合征的表型和突变谱,为该血统的遗传咨询提供了依据。永生化细胞系的建立为进一步研究变异对 IDS 功能的影响和开发靶向药物提供了模型。
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[Clinical phenotype, genetic characteristics, and creation of immortalized cell lines for patients from a pedigree affected with Hunter syndrome].

Objective: To explore the clinical phenotype and genetic variant in a Chinese pedigree affected with Hunter syndrome and create immortalized cell lines for the affected pedigree members.

Methods: A pedigree of six members who had visited Xi'an Children's Hospital in July 2022 was selected as the study subject. Clinical data was collected. Whole exome sequencing was carried out for the pedigree members. Candidate variant was verified by Sanger sequencing. In addition, peripheral B lymphocytes were transfected with Epstein-Barr virus to create immortalized cell lines, which were then subjected to enzyme activity analysis.

Results: The patient, a five-year-and-seven-month-old boy, had exhibited stiff limbs and enlarged joints. He had developed hernia, scaphocephaly, and barrel chest from 3 months of age. His uncle also had stiff limbs, poor hearing, blindness, and right oblique inguinal hernia. Above features had resembled those of Hunter syndrome. Genetic testing revealed that both the child and his uncle had harbored an IDS (NM_000202.8): c.823G>A (p.D275N) variant, which was unreported previously. Bioinformatic analysis indicated that the D275 to be a highly conserved site, and the D275N variant may affect the stability of the protein's spatial conformation, thereby decrease the catalytic activity of the enzyme. The successfully constructed immortalized lymphoblastoid cell lines for the child and his parents showed increased volume, irregular shape, burr structure and cluster growth. And the value of IDS activity of the patient's immortalized lymphoblastoid cells was below the limit of detection. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS3+PM2_Supporting+PM5+PP1+PP3).

Conclusion: Above finding has enriched the phenotypic and mutational spectra of Hunter syndrome, and provided a basis for the genetic counseling for this pedigree. The creation of immortalized cell lines has offered a model for further investigation of the impact of variant on the function of IDS and development of targeted drugs.

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来源期刊
中华医学遗传学杂志
中华医学遗传学杂志 Medicine-Medicine (all)
CiteScore
0.50
自引率
0.00%
发文量
9521
期刊介绍: Chinese Journal of Medical Genetics is a medical journal, founded in 1984, under the supervision of the China Association for Science and Technology, sponsored by the Chinese Medical Association (hosted by Sichuan University), and is now a monthly magazine, which attaches importance to academic orientation, adheres to the scientific, scholarly, advanced, and innovative, and has a certain degree of influence in the industry. Chinese Journal of Medical Genetics is a journal of Peking University, and is now included in Peking University Journal (Chinese Journal of Humanities and Social Sciences), CSCD Source Journals of Chinese Science Citation Database (with extended version), Statistical Source Journals (China Science and Technology Dissertation Outstanding Journals), Zhi.com (in Chinese), Wipu (in Chinese), Wanfang (in Chinese), CA Chemical Abstracts (U.S.), JST (Japan Science and Technology Science and Technology), and JST (Japan Science and Technology Science and Technology Research Center). ), JST (Japan Science and Technology Agency), Pж (AJ) Abstracts Journal (Russia), Copernicus Index (Poland), Cambridge Scientific Abstracts, Abstracts and Citation Database, Abstracts Magazine, Medical Abstracts, and so on.
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