Evidence map›Paper›PMID 40605263›Full record

ArticleMolecular genetics & genomic medicine2025

Novel Loss of Function Variant in SOST From Chinese Family Results in Sclerosteosis 1.

Yufan Guo, Xintao Wu, Yuting Jin, Yu Gu, Yuting Lou, Pu Miao, Ye Wang, Bijun Zhang, Xueting Lin, Chudi Zhang and 1 more

Abstract readCase Reports
In one paragraph

Article in Molecular genetics & genomic medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Yufan GuoDepartment of Pediatrics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.ORCID https://orcid.org/0000-0002-1527-0383
Xintao WuZhejiang University School of Medicine, Hangzhou, China.
Yuting JinDepartment of Pediatrics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Yu GuZhejiang University School of Medicine, Hangzhou, China.
Yuting LouDepartment of Pediatrics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Pu MiaoDepartment of Pediatrics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.ORCID https://orcid.org/0000-0001-5165-2613
Ye WangDepartment of Pediatrics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Bijun ZhangDepartment of Pediatrics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Xueting LinDepartment of Pediatrics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Chudi ZhangDepartment of Pediatrics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Jianhua FengDepartment of Pediatrics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.ORCID https://orcid.org/0000-0002-5849-407X

Funding

Key Research and Development Project of Science and Technology Department of Zhejiang Province 2021C03104National Natural Science Foundation of China 81901383National Natural Science Foundation of China 82101515
6 · The paper itself

Abstract

backgroundSOST encodes a secreted glycoprotein that is similar in sequence to the differential screening-selected gene aberrative in neuroblastoma (DAN) family of bone morphogenetic protein (BMP) antagonists. Pathogenic variants in the SOST gene result in sclerosteosis, van Buchem disease (VBD), or craniodiaphyseal dysplasia. SOST-related genetic disorders are very rare, and limited studies have reported variants associated with sclerosteosis.

methodsClinical tests such as magnetic resonance imaging (MRI), computed tomography (CT), emission computed tomography (ECT), electromyogram (EMG), routine blood tests, and physical examinations were conducted for the proband. Trio-whole exome sequencing (Trio-WES) was performed, and the rare variants (allele frequency < 0.01) in the exon and splicing regions were selected for further pathogenic evaluation. Candidate pathogenic variants were validated through Sanger sequencing. The wild and mutant SOST sequences were cloned into the pcDNA3.1 expression vector, and the RNA and protein expression levels were investigated in the HEK293T cell line.

resultsIn this study, we present a case study of a proband who displays abnormal facial expressions accompanied by numbness. The results of the brain MRI show thickening of the skull and disappearance of the diplopia signal. The temporal bone CT scan indicates diffuse osteosclerosis affecting the bilateral ossicular chains and internal auditory meatus, as well as stenosis of the bilateral internal auditory meatus. Trio-WES sequencing detected a novel homozygous variant in the proband: NM_025237.3(SOST): c.327C>A (p.Cys109*), which was also validated in his sister from the same family. According to the ACMG guidelines, the variant is classified as "likely pathogenic." The in vitro experiments demonstrated that the variant caused a decrease in SOST expression at RNA and protein level and produced a truncated protein.

conclusionThe report presents new evidence for the clinical diagnosis of SOST-related facial numbness and expands the variant spectrum of SOST.

Indexed as

Adaptor Proteins, Signal TransducingHyperostosisLoss of Function MutationAdultEast Asian PeopleFemaleHEK293 CellsHumansMalePedigreeSyndactylyAdaptor Proteins, Signal TransducingSOST protein, humanabnormal facial expressionsfacial numbnessgeneticsclerosteosis 1SOST

Identifiers

PMID40605263
PMCPMC12222177

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.