Evidence map›Paper›PMID 35962790›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2022

Biallelic variants in ADAMTS15 cause a novel form of distal arthrogryposis.

Felix Boschann, Muhsin Ö Cogulu, Davut Pehlivan, Saranya Balachandran, Pedro Vallecillo-Garcia, Christopher M Grochowski, Nils R Hansmeier, Zeynep H Coban Akdemir, Cesar A Prada-Medina, Ayca Aykut and 14 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 35% of its field
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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. ProteinMolecules (Basel, Switzerland) · 2025
    Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 9 institutions in 4 countries.

Felix BoschannInstitute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; RG Development & Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Muhsin Ö CoguluDepartment of Pediatric Genetics, Faculty of Medicine, Ege University, Izmir, Turkey.
Davut PehlivanDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX; Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
Saranya BalachandranInstitute of Human Genetics, University of Lübeck, Lübeck, Germany; Institute of Human Genetics, Kiel University, Kiel, Germany.
Pedro Vallecillo-GarciaInstitute of Biochemistry, Freie University Berlin, Berlin, Germany.
Christopher M GrochowskiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
Nils R HansmeierInstitute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; RG Development & Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany; BIH Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Zeynep H Coban AkdemirDepartment of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, The University of Texas, Houston, TX.
Cesar A Prada-MedinaRG Development & Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Ayca AykutDepartment of Medical Genetics, Faculty of Medicine, Ege University, Izmir, Turkey.
Björn Fischer-ZirnsakInstitute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; RG Development & Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Simon BaduraInterdisciplinary Pediatric Center for Children With Developmental Disabilities and Severe Chronic Disorders, Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Göttingen, Germany.
Burak DurmazDepartment of Pediatric Genetics, Faculty of Medicine, Ege University, Izmir, Turkey.
Ferda OzkinayDepartment of Medical Genetics, Faculty of Medicine, Ege University, Izmir, Turkey.
René HägerlingInstitute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; RG Development & Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany; BIH Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Jennifer E PoseyDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
Sigmar StrickerInstitute of Biochemistry, Freie University Berlin, Berlin, Germany.
Gabriele Gillessen-KaesbachInstitute of Human Genetics, University of Lübeck, Lübeck, Germany.
Malte SpielmannInstitute of Human Genetics, University of Lübeck, Lübeck, Germany; Institute of Human Genetics, Kiel University, Kiel, Germany.
Denise HornInstitute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Knut BrockmannInterdisciplinary Pediatric Center for Children With Developmental Disabilities and Severe Chronic Disorders, Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Göttingen, Germany.
James R LupskiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX.
Uwe KornakInstitute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; RG Development & Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany; Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany. Electronic address: uwe.kornak@med.uni-goettingen.de.
Julia SchmidtInstitute of Human Genetics, University of Lübeck, Lübeck, Germany; Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.
Humboldt-Universität zu Berlin · DEBaylor College of Medicine · USEge University · TRUniversitätsmedizin Göttingen · DEChristian-Albrechts-Universität zu Kiel · DEFreie Universität Berlin · DEMax Planck Institute for Molecular Genetics · DEUniversity of Lübeck · DEUniversity of Texas Health Science Center at Dallas · US

Funding

Baylor-Johns Hopkins Center for Mendelian GeneticsUM1HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2016 to 2020
$14.5M
Frequency of variants of unknown significance by ancestry groups in the All of Us Research Program cohortU01HG011758 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI RICHARD A GIBBS, JAMES R. LUPSKI · 2021 to 2026
$13.8M
Preclinical and Clincial OutcomesP50HD103555 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI Sandesh Chakravarthy Sreenath Nagamani, David Loren Nelson · 2020 to 2026
$9.9M
STRUCTURAL VARIATION IN NEUROLOGICAL DISEASER35NS105078 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI LUPSKI, JAMES R. · 2018 to 2025
$6.0M
MUTATIONAL SIGNATURE(S) OF HUMAN GENOMIC REARRANGEMENT MECHANISMSR01GM106373 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI HASTINGS, PHILIP JOHN, LUPSKI, JAMES R. · 2014 to 2022
$3.1M
Individual genomic analyses to discover the molecular basis and mechanisms contributing to adult-onset diseaseK08HG008986 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI POSEY, JENNIFER ELLEN · 2017 to 2021
$831k
NHGRI NIH HHS K08 HG008986NHGRI NIH HHS U01 HG011758NHGRI NIH HHS UM1 HG006542NICHD NIH HHS P50 HD103555NIGMS NIH HHS R01 GM106373NINDS NIH HHS R35 NS105078
6 · The paper itself

Abstract

purposeWe aimed to identify the underlying genetic cause for a novel form of distal arthrogryposis.

methodsRare variant family-based genomics, exome sequencing, and disease-specific panel sequencing were used to detect ADAMTS15 variants in affected individuals. Adamts15 expression was analyzed at the single-cell level during murine embryogenesis. Expression patterns were characterized using in situ hybridization and RNAscope.

resultsWe identified homozygous rare variant alleles of ADAMTS15 in 5 affected individuals from 4 unrelated consanguineous families presenting with congenital flexion contractures of the interphalangeal joints and hypoplastic or absent palmar creases. Radiographic investigations showed physiological interphalangeal joint morphology. Additional features included knee, Achilles tendon, and toe contractures, spinal stiffness, scoliosis, and orthodontic abnormalities. Analysis of mouse whole-embryo single-cell sequencing data revealed a tightly regulated Adamts15 expression in the limb mesenchyme between embryonic stages E11.5 and E15.0. A perimuscular and peritendinous expression was evident in in situ hybridization in the developing mouse limb. In accordance, RNAscope analysis detected a significant coexpression with Osr1, but not with markers for skeletal muscle or joint formation.

conclusionIn aggregate, our findings provide evidence that rare biallelic recessive trait variants in ADAMTS15 cause a novel autosomal recessive connective tissue disorder, resulting in a distal arthrogryposis syndrome.

Indexed as

ArthrogryposisContractureADAMTS ProteinsAnimalsConsanguinityHomozygoteHumansMiceMutationPedigreePhenotypeADAMTS15 protein, humanADAMTS15 protein, mouseADAMTS ProteinsADAMTS15Connective tissueDistal arthrogryposisExome sequencing

Identifiers

PMID35962790
PMCPMC9982667
OpenAlexW4291129572

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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.