病例报告： 全外显子组测序发现一名发育迟缓男性的 HPRT1 基因存在新型变异

Case report: Whole exome sequencing identifies a novel variant in the HPRT1 gene in a male with developmental delay

病例报告： 全外显子组测序发现一名发育迟缓男性的 HPRT1 基因存在新型变异

Authors: Haoyang Zheng, Gui Chen, Tingting Wang, Weisheng Cheng, Jing Yuan, Fang Liu, Yuanhong Xu

Source: Frontiers in Genetics

DOI: 10.3389/fgene.2025.1512070

Abstract

Lesch-Nyhan syndrome (LNS, OMIM #300322) is a rare X-linked genetic disorder caused by variants in the HPRT1 gene, which codes for the Hypoxanthine-guanine phosphoribosyltransferase (HGPRT). HPRT1 gene variants disrupt normal purine metabolism, leading to the involvement of multiple organ systems, primarily characterized by hyperuricemia, dystonia, and neurological abnormalities, which makes LNS clinically heterogeneous and diagnostically challenging. Here, we report a rare case of a 27-year-old Chinese male exhibiting severe lower limb motor disorders, hyperuricemia, and intellectual development delay. Blood tests showed hyperuricemia and whole exome sequencing (WES) identified a novel hemizygous variant in the HPRT1 (NM-000194.3) gene: c.104T > C in exon 2, respectively. Bioinformatics techniques indicated that the variant may disrupt the activity of HGPRT. According to the clinical presentation, diagnostic examination, and WES results, the patient was finally diagnosed with LNS. This study identified a previously unreported pathogenic variant in the HPRT1 gene. Although no curative therapy is currently available for HPRT1 gene variants at present, a definite diagnosis of its genetic etiology is of great significance for genetic counseling and family planning.

Keywords: HGPRT; HPRT1; X-linked disease; lesch-nyhan syndrome; novel variant.

摘要

莱施-奈恩综合征（LNS，OMIM #300322）是一种罕见的X连锁遗传疾病，由编码次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HGPRT）的HPRT1基因变异引起。HPRT1 基因变异会破坏正常的嘌呤代谢，导致多个器官系统受累，主要表现为高尿酸血症、肌张力障碍和神经系统异常，这使得 LNS 具有临床异质性和诊断挑战性。本文报告了一例罕见病例，患者为一名 27 岁的中国男性，表现为严重的下肢运动障碍、高尿酸血症和智力发育迟缓。血检显示患者患有高尿酸血症，全外显子组测序（WES）发现了 HPRT1（NM-000194.3）基因中的一个新型半杂合子变异：第 2 外显子中的 c.104T > C。生物信息学技术表明，该变异可能会破坏 HGPRT 的活性。根据临床表现、诊断检查和 WES 结果，患者最终被确诊为 LNS。这项研究在 HPRT1 基因中发现了一种之前未报道过的致病变异。虽然目前还没有针对 HPRT1 基因变异的治疗方法，但明确诊断其遗传病因对遗传咨询和计划生育具有重要意义。

关键词: HGPRT；HPRT1；X连锁病；莱希-尼汉综合征；新型变体