Objective To describe clinical, radiological, biochemical, and genetic features in a multigenerational family with HPRT1-related gout and highlight intrafamilial phenotypic variation. Methods Seven family members underwent clinical, laboratory, radiological, and genetic evaluation. Clinical exome sequencing was performed in the index case, followed by targeted Sanger sequencing in available relatives. Dual-energy computed tomography was used to detect monosodium urate deposition in clinically suspected joints. Results Seven patients from the same family were evaluated; five had genetically confirmed HPRT1 (NM_000194.3) c.481G > T (p.Ala161Ser), while pedigree and clinical findings strongly supported the same diagnosis in two others. Four were male, and three were female. Male patients showed earlier onset, frequent attacks, marked hyperuricemia, universal tophus formation, and greater structural damage. Female carriers generally had milder manifestations, although one developed clinically overt gout. Imaging demonstrated bilateral sacroiliitis in two patients and widespread urate deposits in peripheral joints. Older affected individuals had destructive disease, including amputations. Conclusion Pathogenic HPRT1 variants may cause markedly different phenotypes within a single family, from mild hyperuricemia to severe early-onset gout with complications. Early-onset or familial gout should prompt HPRT1 disease evaluation; early molecular diagnosis and family screening may help prevent permanent joint damage by clarifying clinical risks. <Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="justify" colname="c1" colnum="1" /> <colspec align="justify" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> Key Points • The same HPRT1 mutation can cause marked intrafamilial clinical and radiological variability.  • Early-onset or familial gout should raise suspicion for HPRT1-related disease. • Early molecular diagnosis and family screening may prevent irreversible joint damage. </entry> </row> </tbody> </tgroup> </Table>

Same mutation, different disease: intrafamilial clinical and radiological diversity in HPRT1-related gout—the first family series from Türkiye

期刊论文
发表日期：

2026年7月28日

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Reyhan Bilici,
Fahrettin Duymus,
Abdullah Enes Atas,
Selma Özlem Celikdelen

摘要

Objective

To describe clinical, radiological, biochemical, and genetic features in a multigenerational family with HPRT1-related gout and highlight intrafamilial phenotypic variation.

Methods

Seven family members underwent clinical, laboratory, radiological, and genetic evaluation. Clinical exome sequencing was performed in the index case, followed by targeted Sanger sequencing in available relatives. Dual-energy computed tomography was used to detect monosodium urate deposition in clinically suspected joints.

Results

Seven patients from the same family were evaluated; five had genetically confirmed HPRT1 (NM_000194.3) c.481G > T (p.Ala161Ser), while pedigree and clinical findings strongly supported the same diagnosis in two others. Four were male, and three were female. Male patients showed earlier onset, frequent attacks, marked hyperuricemia, universal tophus formation, and greater structural damage. Female carriers generally had milder manifestations, although one developed clinically overt gout. Imaging demonstrated bilateral sacroiliitis in two patients and widespread urate deposits in peripheral joints. Older affected individuals had destructive disease, including amputations.

Conclusion

Pathogenic HPRT1 variants may cause markedly different phenotypes within a single family, from mild hyperuricemia to severe early-onset gout with complications. Early-onset or familial gout should prompt HPRT1 disease evaluation; early molecular diagnosis and family screening may help prevent permanent joint damage by clarifying clinical risks.

Key Points

• The same HPRT1 mutation can cause marked intrafamilial clinical and radiological variability.

• Early-onset or familial gout should raise suspicion for HPRT1-related disease.

• Early molecular diagnosis and family screening may prevent irreversible joint damage.