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

Haoyang Zheng ^1,2,3 Gui Chen ^1,2,3 Tingting Wang ^4* Weisheng Cheng ^10,5,6,7,8,9 Jing Yuan ^{10,5,6,7,8,9*} Fang Liu ^1,2,3* Yuanhong XU ^1,2,3*

• ¹ Department of Laboratory Medicine, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
• ² Anhui Key Laboratory of Infectious Diseases of Animal Origin, Anhui Medical University,, Hefei, Anhui Province, China
• ³ Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei, Anhui Province, China
• ⁴ Huangling Town Health Center, Linquan County, Fuyang, Jiangsu Province, China
• ⁵ Prenatal Diagnostic Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
• ⁶ NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
• ⁷ Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, Hefei, Anhui Province, China
• ⁸ MOE Key Laboratory of Population Health Across Life Cycle, Hefei, Anhui Province, China
• ⁹ Anhui Province Key Laboratory of Reproductive Disorders and Obstetrics and Gynecology Diseases, Anhui Medical University, Hefei, Anhui Province, China
• ¹⁰ Anhui Provincial Institute of Translational Medicine, Hefei, Anhui Province, China

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.