Evidence map›Paper›PMID 31587868›Full record

ArticleAmerican journal of human genetics2019

Missense Mutations in NKAP Cause a Disorder of Transcriptional Regulation Characterized by Marfanoid Habitus and Cognitive Impairment.

Sarah K Fiordaliso, Aiko Iwata-Otsubo, Alyssa L Ritter, Mathieu Quesnel-Vallières, Katsunori Fujiki, Eriko Nishi, Miroslava Hancarova, Noriko Miyake, Jenny E V Morton, Sangmoon Lee and 27 more

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

Article in American journal of human genetics, 2019. 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
0.7field-weighted citation impact, top 24% 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, 17 citations in OpenAlex.

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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

37 authors at 12 institutions in 8 countries.

Sarah K FiordalisoDivision of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Aiko Iwata-OtsuboDivision of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Alyssa L RitterDivision of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Mathieu Quesnel-VallièresDepartment of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Katsunori FujikiLaboratory of Genome Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-8657, Japan.
Eriko NishiDivision of Medical Genetics, Nagano Children's Hospital, Azumino 399-8205, Japan.
Miroslava HancarovaDepartment of Biology and Medical Genetics, 2nd Faculty of Medicine and University Hospital Motol, Charles University, Prague 15006, Czech Republic.
Noriko MiyakeDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Jenny E V MortonWest Midlands Regional Clinical Genetics Service and Birmingham Health Partners, Birmingham Women's and Children's Hospitals NHS Foundation Trust, Edbaston, Birmingham B15 2TG, UK.
Sangmoon LeeDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Karl HackmannInstitute for Clinical Genetics, TU Dresden, Dresden 01307, Germany.
Masashige BandoLaboratory of Genome Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-8657, Japan.
Koji MasudaLaboratory of Genome Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-8657, Japan.
Ryuichiro NakatoLaboratory of Genome Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-8657, Japan.
Michiko ArakawaDivision of Medical Genetics, Nagano Children's Hospital, Azumino 399-8205, Japan.
Elizabeth BhojDivision of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Dong LiCenter for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Hakon HakonarsonDivision of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Ryojun TakedaDivision of Medical Genetics, Nagano Children's Hospital, Azumino 399-8205, Japan.
Margaret HarrCenter for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Beth KeenaDivision of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Elaine H ZackaiDivision of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Nobuhiko OkamotoDepartment of Medical Genetics, Osaka Women's and Children's Hospital, Osaka 594-1101, Japan.
Seiji MizunoDepartment of Clinical Genetics, Central Hospital, Aichi Developmental Disability Center, Aichi 480-0304, Japan.
Jung Min KoDepartment of Pediatrics, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Alica ValachovaDepartment of Medical Genetics, University Hospital Trencin, Trencin 91171, Slovakia.
Darina PrchalovaDepartment of Biology and Medical Genetics, 2nd Faculty of Medicine and University Hospital Motol, Charles University, Prague 15006, Czech Republic.
Marketa VlckovaDepartment of Biology and Medical Genetics, 2nd Faculty of Medicine and University Hospital Motol, Charles University, Prague 15006, Czech Republic.
Tommaso PippucciMedical Genetics Unit, Policlinico Sant'Orsola-Malpighi, University of Bologna, Bologna 40138, Italy.
Christoph SeilerZebrafish Core Facility, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Murim ChoiDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Pediatrics, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Naomichi MatsumotoDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Nataliya Di DonatoInstitute for Clinical Genetics, TU Dresden, Dresden 01307, Germany.
Yoseph BarashDepartment of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Zdenek SedlacekDepartment of Biology and Medical Genetics, 2nd Faculty of Medicine and University Hospital Motol, Charles University, Prague 15006, Czech Republic.
Katsuhiko ShirahigeLaboratory of Genome Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-8657, Japan.
Kosuke IzumiDivision of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Laboratory of Rare Disease Research, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-8657, Japan. Electronic address: izumik1@email.chop.edu.
Children's Hospital of Philadelphia · USThe University of Tokyo · JPCharles University · CZNagano Children's Hospital · JPSeoul National University · KRTechnische Universität Dresden · DEUniversity of Pennsylvania · USYokohama City University · JPAichi Developmental Disability Center · JPBirmingham Women’s and Children’s NHS Foundation Trust · GBIRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola · ITOsaka Women's and Children's Hospital · JP

Funding

The Intellectual and Developmental Disabilities Research Center at CHOP/PennU54HD086984 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI PUTT, MARY E. · 2016 to 2020
$6.3M
NICHD NIH HHS U54 HD086984
6 · The paper itself

Abstract

NKAP is a ubiquitously expressed nucleoplasmic protein that is currently known as a transcriptional regulatory molecule via its interaction with HDAC3 and spliceosomal proteins. Here, we report a disorder of transcriptional regulation due to missense mutations in the X chromosome gene, NKAP. These mutations are clustered in the C-terminal region of NKAP where NKAP interacts with HDAC3 and post-catalytic spliceosomal complex proteins. Consistent with a role for the C-terminal region of NKAP in embryogenesis, nkap mutant zebrafish with a C-terminally truncated NKAP demonstrate severe developmental defects. The clinical features of affected individuals are highly conserved and include developmental delay, hypotonia, joint contractures, behavioral abnormalities, Marfanoid habitus, and scoliosis. In affected cases, transcriptome analysis revealed the presence of a unique transcriptome signature, which is characterized by the downregulation of long genes with higher exon numbers. These observations indicate the critical role of NKAP in transcriptional regulation and demonstrate that perturbations of the C-terminal region lead to developmental defects in both humans and zebrafish.

Indexed as

Amino Acid SequenceAnimalsCognitive DysfunctionDown-RegulationExonsGene Expression RegulationGenes, X-LinkedHistone Deacetylase 3Histone DeacetylasesHumansMutation, MissenseRepressor ProteinsSequence AlignmentTranscription, GeneticTranscriptomeZebrafishHistone Deacetylase 3Histone DeacetylasesNKAP protein, humanRepressor ProteinsP-complexspliceosomesplicingtranscriptome

Identifiers

PMID31587868
PMCPMC6848994
OpenAlexW2977373824

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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 OpenQuestion graph.