Evidence map›Paper›PMID 34040189›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021

UBA2 variants underlie a recognizable syndrome with variable aplasia cutis congenita and ectrodactyly.

Rhonda E Schnur, Sairah Yousaf, James Liu, Wendy K Chung, Lindsay Rhodes, Michael Marble, Regina M Zambrano, Nara Sobreira, Parul Jayakar, Mary Ella Pierpont and 17 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

12 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
  2. Case Report: A newFrontiers in medicine · 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

27 authors at 12 institutions in 3 countries.

Rhonda E Schnur *Clinical Genomics Program, GeneDx, Gaithersburg, MD, USA. rschnur@genedx.com.
Sairah Yousaf *National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
James Liu *National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Wendy K ChungDivision of Clinical Genetics, Departments of Pediatrics and Medicine, Columbia University, New York, NY, USA.
Lindsay RhodesClinical Genomics Program, GeneDx, Gaithersburg, MD, USA.
Michael MarbleDepartment of Pediatrics, Division of Pediatric Genetics, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Regina M ZambranoDepartment of Pediatrics, Division of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
Nara SobreiraMcKusick-Nathans Department of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA.
Parul JayakarDivision of Genetics and Metabolism, Nicklaus Children's Hospital, Miami, FL, USA.
Mary Ella PierpontDepartments of Pediatrics and Ophthalmology, University of Minnesota Medical School, Minneapolis, MN, USA.
Matthew J SchultzDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Pavel N PichurinDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Rory J OlsonDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Gail E GrahamDivision of Genetics, Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
Matthew OsmondChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
Gustavo A Contreras-GarcíaDivision de Genética Médica, Departamento de Pediatría-Hospital Universitario de Santander, Departamento de Ciencias Básicas, Grupo de Investigación en Genética Humana UIS, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia.
Karina A Campo-NeiraSemillero de Investigación en Genética Humana SIGENH, Escuela de Medicina, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia.
Camilo A Peñaloza-MantillaSemillero de Investigación en Genética Humana SIGENH, Escuela de Medicina, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia.
Mark FlageNational Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Srikar KuppaNational Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Karina NavarroNational Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Maria J Guillen SacotoClinical Genomics Program, GeneDx, Gaithersburg, MD, USA.
Ingrid M WentzensenClinical Genomics Program, GeneDx, Gaithersburg, MD, USA.
Maria I ScaranoDivision of Genetics, Department of Pediatrics, Cooper Medical School of Rowan University, Cooper University Health Care, Camden, NJ, USA.
Jane JuusolaClinical Genomics Program, GeneDx, Gaithersburg, MD, USA.
Carlos E PradaDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Robert B HufnagelNational Eye Institute, National Institutes of Health, Bethesda, MD, USA. robert.hufnagel@nih.gov.ORCID 0000-0003-3015-3545
National Institutes of Health · USIndustrial University of Santander · COMayo Clinic in Arizona · USCooper Medical School of Rowan University · USUniversity of Ottawa · CACincinnati Children's Hospital Medical Center · USJohns Hopkins University · USLouisiana State University Health Sciences Center New Orleans · USMiami Children's Hospital · USPediatrics and Genetics · USUniversity of Minnesota Medical Center · USUniversity of New Mexico · US

Funding

Baylor-Johns Hopkins Center for Mendelian GeneticsU54HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2012 to 2015
$15.6M
Genomic and epigenomic mechanisms of pediatric ocular disordersZIAEY000565 · NEI · NATIONAL EYE INSTITUTE · PI HUFNAGEL, ROBERT · 2019 to 2024
$11.4M
Clinical ophthalmic molecular diagnostics and discoveryZIAEY000564 · NEI · NATIONAL EYE INSTITUTE · PI GUAN, BIN · 2019 to 2025
$7.9M
Intramural NIH HHS ZIA EY000564Intramural NIH HHS ZIA EY000565NHGRI NIH HHS U54 HG006542
6 · The paper itself

Abstract

purposeThe human chromosome 19q13.11 deletion syndrome is associated with a variable phenotype that includes aplasia cutis congenita (ACC) and ectrodactyly as specific features. UBA2 (ubiquitin-like modifier-activating enzyme 2) lies adjacent to the minimal deletion overlap region. We aimed to define the UBA2-related phenotypic spectrum in humans and zebrafish due to sequence variants and to establish the mechanism of disease.

methodsExome sequencing was used to detect UBA2 sequence variants in 16 subjects in 7 unrelated families. uba2 loss of function was modeled in zebrafish. Effects of human missense variants were assessed in zebrafish rescue experiments.

resultsSeven human UBA2 loss-of-function and missense sequence variants were detected. UBA2-phenotypes included ACC, ectrodactyly, neurodevelopmental abnormalities, ectodermal, skeletal, craniofacial, cardiac, renal, and genital anomalies. uba2 was expressed in zebrafish eye, brain, and pectoral fins; uba2-null fish showed deficient growth, microcephaly, microphthalmia, mandibular hypoplasia, and abnormal fins. uba2-mRNAs with human missense variants failed to rescue nullizygous zebrafish phenotypes.

conclusionUBA2 variants cause a recognizable syndrome with a wide phenotypic spectrum. Our data suggest that loss of UBA2 function underlies the human UBA2 monogenic disorder and highlights the importance of SUMOylation in the development of affected tissues.

Indexed as

Abnormalities, MultipleEctodermal DysplasiaLimb Deformities, CongenitalAnimalsHumansUbiquitin-Activating EnzymesZebrafishUBA2 protein, humanUbiquitin-Activating Enzymes

Identifiers

PMID34040189
PMCPMC8463496
OpenAlexW3164885305

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.