Evidence map›Paper›PMID 39615461›Full record

ArticleEBioMedicine2024

Homozygous variant in translocase of outer mitochondrial membrane 7 leads to metabolic reprogramming and microcephalic osteodysplastic dwarfism with moyamoya disease.

Chia-Yi Li, Li-Wen Chen, Meng-Che Tsai, Yen-Yin Chou, Pei-Xuan Lin, Yu-Ming Chang, Wuh-Liang Hwu, Yin-Hsiu Chien, Ju-Li Lin, Hui-An Chen and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

6 citing papers in PubMed.

  1. From the cytosol to the inner membrane: biogenesis of the mitochondrial carrier family.Protein science : a publication of the Protein Society · 2026
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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

22 authors.

Chia-Yi LiInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Li-Wen ChenDepartment of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Meng-Che TsaiInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Genomic Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Yen-Yin ChouDepartment of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Genomic Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Pei-Xuan LinInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Yu-Ming ChangDepartment of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Wuh-Liang HwuPrecision Medical Center, China Medical University Hospital, Taichung City, Taiwan; Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
Yin-Hsiu ChienDepartment of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Ju-Li LinDepartment of Pediatrics, Chang Gung Memorial Hospital, Linkou, Taiwan.
Hui-An ChenDepartment of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Ni-Chung LeeDepartment of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Pen-Hua SuDepartment of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Tzung-Chien HsiehInstitute for Genomic Statistics and Bioinformatics, Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
Hannah KlinkhammerInstitute for Genomic Statistics and Bioinformatics, Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany; Institute for Medical Biometry, Informatics and Epidemiology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
Yi-Chieh WangInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Yi-Ting HuangInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Peter M KrawitzInstitute for Genomic Statistics and Bioinformatics, Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
Sheng-Hsiang LinInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Lynn L H HuangInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwan.
Po-Min ChiangInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Min-Hsiu ShihDepartment of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Peng-Chieh ChenInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: pengchic@mail.ncku.edu.tw.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImpaired mitochondrial protein import machinery leads to phenotypically heterogeneous diseases. Here, we report a recurrent homozygous missense variant in the gene that encodes the translocase of outer mitochondrial membrane 7 (TOMM7) in nine patients with microcephaly, short stature, facial dysmorphia, atrophic macular scarring, and moyamoya disease from seven unrelated families.

methodsTo prove the causality of the TOMM7 variant, mitochondrial morphology, proteomics, and respiration were investigated in CRISPR/Cas9-edited iPSCs-derived endothelial cells. Cerebrovascular defects and mitochondrial respiration were also examined in CRISPR/Cas9-edited zebrafish.

findingsiPSC-derived endothelial cells with homozygous TOMM7 p.P29L showed increased TOM7 stability, enlarged mitochondria, increased senescence, and defective tube formation. In addition, proteomic analysis revealed a reduced abundance of mitochondrial proteins involved in ATP synthesis or coordinating TCA cycle and gluconeogenesis. Moreover, mitochondrial respiration was slightly decreased while ATP production from glycolysis was significantly increased. Furthermore, deletion of tomm7 in zebrafish caused craniofacial and cerebrovascular defects that recapitulated human phenotypes. Notably, homozygous iPSCs differentially expressed genes involved in glycolysis and response to hypoxia. Finally, the metabolic imbalance was evidenced by decreased oxygen consumption, increased level of hexokinase 2, and enhanced glycolysis in endothelial cells derived from the patient's iPSCs.

interpretationThese results revealed the essential role of TOMM7 in balancing cellular sources of energy production at both proteomic and transcriptomic levels and provided the molecular mechanisms through which TOMM7 p.P29L variant leads to an autosomal recessive microcephalic osteodysplastic dwarfism with moyamoya disease.

fundingThis work is supported by National Science and Technology Council grants and National Cheng Kung University Hospital.

Indexed as

HomozygoteMicrocephalyMoyamoya DiseaseZebrafishAnimalsChildChild, PreschoolCRISPR-Cas SystemsDisease Models, AnimalDwarfismEndothelial CellsFemaleHumansInduced Pluripotent Stem CellsMaleMetabolic ReprogrammingMitochondrial Precursor Protein Import Complex ProteinsCerebrovascular diseaseGlycolysisiPSC-derived endothelial cellsMitochondrial protein importMitochondrial respirationTOM complex

Identifiers

PMID39615461
PMCPMC11648121

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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 OpenQuestion graph.