Evidence map›Paper›PMID 40304391›Full record

ArticleBirth defects research2025

Exome Sequencing to Identify Novel Susceptibility Genes for Nonsyndromic Split-Hand/Ft Malformation: A Report From the National Birth Defects Prevention Study.

Tonia C Carter, Denise M Kay, Faith Pangilinan, Lynn M Almli, Mary M Jenkins, Elizabeth E Blue, Pagna Sok, Janson J White, Christopher M Cunniff, A J Agopian and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Birth defects research, 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

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

1 citing paper in PubMed.

  1. Review
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

30 authors.

Tonia C CarterCenter for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, Wisconsin, USA.ORCID https://orcid.org/0000-0002-2107-7838
Denise M KayDivision of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.ORCID https://orcid.org/0000-0002-9928-2698
Faith PangilinanGenetics and Environment Interaction Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.ORCID https://orcid.org/0000-0003-0486-1134
Lynn M AlmliNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Mary M JenkinsNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.ORCID https://orcid.org/0000-0002-4399-1348
Elizabeth E BlueDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington, USA.ORCID https://orcid.org/0000-0002-0633-0305
Pagna SokDepartment of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas, USA.
Janson J WhiteDepartment of Pediatrics, University of Washington, Seattle, Washington, USA.
Christopher M CunniffDepartment of Pediatrics, Weill Cornell Medical Center, New York, New York, USA.
A J AgopianDepartment of Epidemiology, Human Genetics Center, University of Texas School of Public Health, Houston, Texas, USA.ORCID https://orcid.org/0000-0002-5874-4155
Michael J BamshadBrotman Baty Institute for Precision Medicine, Seattle, Washington, USA.
Lorenzo D BottoDivision of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
Lawrence C BrodyGenetics and Environment Interaction Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Muge Gucsavas-CalikogluDepartment of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Jessica X ChongBrotman Baty Institute for Precision Medicine, Seattle, Washington, USA.
Horacio Gomez-AcevedoDepartment of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.ORCID https://orcid.org/0000-0002-1570-1606
Philip J LupoDepartment of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas, USA.ORCID https://orcid.org/0000-0003-0978-5863
Cynthia A MooreNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.ORCID https://orcid.org/0000-0003-4224-2692
Wendy N NembhardFay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.ORCID https://orcid.org/0000-0002-8318-4049
Richard S OlneyDepartment of Epidemiology, College of Public Health, The University of Iowa, Iowa City, Iowa, USA.
Andrew F OlshanDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0001-9115-5128
Mohammed S OrloffFay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Jennita ReefhuisNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.ORCID https://orcid.org/0000-0002-4747-4831
Paul A RomittiDepartment of Epidemiology, College of Public Health, The University of Iowa, Iowa City, Iowa, USA.ORCID https://orcid.org/0000-0001-5393-9984
Gary M ShawDepartment of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.ORCID https://orcid.org/0000-0001-7438-4914
Martha M WerlerDepartment of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA.
Mahsa M YazdyMassachusetts Department of Public Health, Boston, Massachusetts, USA.ORCID https://orcid.org/0000-0002-7415-5350
Marilyn L BrowneBirth Defects Registry, New York State Department of Health, Albany, New York, USA.ORCID https://orcid.org/0000-0002-1872-2787
Meredith M HowleyBirth Defects Registry, New York State Department of Health, Albany, New York, USA.ORCID https://orcid.org/0000-0002-8420-5040
University of Washington Center for Mendelian Genomics, NISC Comparative Sequencing Program, the National Birth Defects Prevention Study

Funding

UW Center for Mendelian GenomicsUM1HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, LEAL, SUZANNE M · 2016 to 2020
$15.3M
NHGRI Genome Sequencing Program Coordinating CenterU24HG008956 · NHGRI · RUTGERS, THE STATE UNIV OF N.J. · PI BUYSKE, STEVEN G, MATISE, TARA C. · 2016 to 2020
$4.9M
ACL HHS U01DD001304ACL HHS U01DD001309CDC HHSIntramural CDC HHS CC999999Marshfield Clinic Research FoundationNCBDD CDC HHS U01 DD001304NCBDD CDC HHS U01 DD001309NHGRI NIH HHS U24 HG008956NHGRI NIH HHS UM1 HG006493NHLBI NIH HHS
6 · The paper itself

Abstract

backgroundSplit-hand/foot malformation (SHFM) is a rare, genetically heterogeneous, congenital limb defect. Some but not all associated genes are known; therefore, the aim was to identify genes underlying SHFM.

methodsBuccal cell-derived DNA from 26 children with SHFM and their parents who participated in the National Birth Defects Prevention Study was exome sequenced. Family-based trio analyzes prioritized rare coding variants by inheritance patterns, predicted pathogenicity, and location within putative limb development genes. Copy-number variants in SHFM candidate genomic regions were also examined. Case-control analyzes compared coding variants between case children and 1191 controls (parents of children with non-limb birth defects). Variant validation was by Sanger sequencing or droplet digital polymerase chain reaction.

resultsIn family-based analyzes, the prioritized and validated variants (each in a single family) included likely damaging variants that were heterozygous and de novo in speckle type BTB/POZ protein (SPOP) and ubiquitin-like modifier activating enzyme 2 (UBA2), X-linked recessive in fibroblast growth factor 13 (FGF13) and RNA binding motif protein 10 (RBM10), and compound heterozygous in interleukin enhancer binding factor 3 (ILF3). Validation assays did not confirm predicted de novo copy-number gains at chromosomes 10q24 and 19p13.11. Case-control analyzes did not identify statistically significant associations.

conclusionExome analysis nominated new susceptibility genes (FGF13, ILF3, RBM10, SPOP) and detected a variant in a known candidate gene (UBA2). Follow-up investigation is needed to ascertain damaging variants in these genes in additional cases with SHFM and evaluate the impact of the variants on gene expression, protein function, and limb development.

Indexed as

Genetic Predisposition to DiseaseLimb Deformities, CongenitalCase-Control StudiesDNA Copy Number VariationsExomeExome SequencingFemaleHumansMalebirth defectscongenital limb malformationectrodactylyexome sequencingNBDPSsplit footsplit hand

Identifiers

PMID40304391
PMCPMC12818101

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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.