Juvenile Paget disease with unique compound heterozygous sequence variants in the TNFRSF11B gene

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10500456" target="_blank" >RIV/00179906:_____/25:10500456 - isvavai.cz</a>

Alternative codes found

RIV/60162694:G44__/26:00564499 RIV/00216208:11120/25:43928700 RIV/00216208:11150/25:10500456 RIV/65269705:_____/25:00082396 RIV/00064173:_____/25:43928700

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=g_VukoD1bG" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=g_VukoD1bG</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s13023-025-03804-2" target="_blank" >10.1186/s13023-025-03804-2</a>

Result language

angličtina

Original language name

Juvenile Paget disease with unique compound heterozygous sequence variants in the TNFRSF11B gene

Original language description

Background: Juvenile Paget disease (JPD) is a rare autosomal recessive bone disease characterized by escalated bone metabolism leading to skeletal deformities, susceptibility to fractures, and some extraskeletal findings. This genetic disease is associated with changes in the TNFRSF11B gene encoding osteoprotegerin, an important regulator of osteoresorption. Most published JPD cases have been found to carry homozygous TNFRSF11B variants, while compound heterozygous variants in this gene have been reported only twice. Methods and results: We report the first case of JPD diagnosed in the Czech Republic, who presented with a mild phenotype of this disease. The first bone fractures, appeared at 3 years of age. Other clinical manifestations included typical skeletal deformities, macrocephaly, arched chest, lower extremity valgosity, lateral bowing of the thighs, and anterior bowing of the shins. Minor mixed hearing impairment, angioid stripes of the choroidea, and temporary immunodeficiency were present among extra-skeletal findings. Sanger sequencing was performed on both the patient and the parents to test for the presence of TNFRSF11B sequence variants. Molecular genetic analysis showed unique compound heterozygous sequence variants in TNFRSF11B: a paternally inherited variant c.30 + 5G &gt; A, p.(?) and a maternally inherited variant c.329G &gt; T, p.(Gly110Val). Both of the variants were analyzed by several in silico predictive tools indicating, for their strongly supported pathogenicity according to American College of Medical Genetics and Genomics standards. Furthermore, we present diagnostic findings, their treatment, and follow-up care. Conclusion: The newly described variants of TNFRSF11B extend knowledge of this very rare disease. Early diagnosis and antiresorption treatment prevent further fractures and deformity progression, and improve the patient&apos;s quality of life. This example of osteoprotegerin deficiency may help us better understand its role in skeletal and non-skeletal systems.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Orphanet Journal of Rare Diseases

ISSN

1750-1172

e-ISSN

1750-1172

Volume of the periodical

20

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

8

Pages from-to

409

UT code for WoS article

001546828900008

EID of the result in the Scopus database

2-s2.0-105012749710