Evidence map›Paper›PMID 31585108›Full record

ArticleAmerican journal of human genetics2019

Bi-allelic Loss of Human APC2, Encoding Adenomatous Polyposis Coli Protein 2, Leads to Lissencephaly, Subcortical Heterotopia, and Global Developmental Delay.

Sangmoon Lee, Dillon Y Chen, Maha S Zaki, Reza Maroofian, Henry Houlden, Nataliya Di Donato, Dalia Abdin, Heba Morsy, Ghayda M Mirzaa, William B Dobyns and 14 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 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.7field-weighted citation impact, top 18% 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

9 citing papers in PubMed, 23 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

24 authors at 14 institutions in 8 countries.

Sangmoon LeeDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, CA 92093, USA; Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA 92123, USA.
Dillon Y ChenDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, CA 92093, USA; Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA 92123, USA.
Maha S ZakiClinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo 12311, Egypt.
Reza MaroofianGenetics Research Centre, Molecular and Clinical Sciences Institute, St. George's University, London SW17 0RE, UK; Department of Neuromuscular Disorders, University College London Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Henry HouldenDepartment of Neuromuscular Disorders, University College London Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Nataliya Di DonatoInstitute for Clinical Genetics, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Dalia AbdinInstitute for Clinical Genetics, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany; Human Cytogenetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo 12311, Egypt.
Heba MorsyHuman Genetics Department, Medical Research Institute, Alexandria University, Alexandria 21561, Egypt.
Ghayda M MirzaaCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA; Department of Pediatrics, University of Washington, Seattle Children's Research Institute, Seattle WA, 98101, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA.
William B DobynsCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA; Department of Pediatrics, University of Washington, Seattle Children's Research Institute, Seattle WA, 98101, USA; Department of Neurology, University of Washington, Seattle Children's Research Institute, Seattle WA, 98101, USA.
Jennifer McEvoy-VenneriDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, CA 92093, USA.
Valentina StanleyDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, CA 92093, USA.
Kiely N JamesDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, CA 92093, USA.
Grazia M S ManciniDepartment of Clinical Genetics, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands.
Rachel SchotDepartment of Clinical Genetics, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands.
Tugba KalayciDepartment of Clinical Genetics, Erasmus University Medical Center, 3015 CN Rotterdam, the Netherlands; Department of Medical Genetics, Istanbul University, Istanbul Faculty of Medicine, Istanbul 34093, Turkey.
Umut AltunogluDepartment of Medical Genetics, Istanbul University, Istanbul Faculty of Medicine, Istanbul 34093, Turkey.
Ehsan Ghayoor KarimianiGenetics Research Centre, Molecular and Clinical Sciences Institute, St. George's University, London SW17 0RE, UK.
Lauren BrickDepartment of Genetics, McMaster Children's Hospital, Hamilton, Ontario L8S 4L8, Canada.
Mariya KozenkoDepartment of Genetics, McMaster Children's Hospital, Hamilton, Ontario L8S 4L8, Canada.
Yalda JamshidiGenetics Research Centre, Molecular and Clinical Sciences Institute, St. George's University, London SW17 0RE, UK.
M Chiara ManziniChild Health Institute of New Jersey, Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
Mehran Beiraghi ToosiDepartment of Pediatric Neurology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad 7HRJ+HQ, Iran.
Joseph G GleesonDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, CA 92093, USA; Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA 92123, USA. Electronic address: jogleeson@ucsd.edu.
Howard Hughes Medical Institute · USErasmus MC · NLMcMaster Children's Hospital · CARady Children's Hospital-San Diego · USSt George's, University of London · GBTU Dresden · DEUniversity College London · GBAlexandria University · EGBrotman Baty Institute · USGhaem Hospital · IRIstanbul University · TRNational Research Centre · EGRutgers, The State University of New Jersey · USUniversity of Washington · US

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5M
Yale Center for Mendelian DisordersU54HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2012 to 2015
$11.0M
Molecular Characterization of Joubert SyndromeR01NS048453 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2004 to 2020
$6.0M
Mosaicism in focal cortical dysplasias spectrum seen in neuropsychiatric diseaseU01MH108898 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2015 to 2019
$5.1M
SIGNAL TRANSDUCTION PATHWAYS FOR NEURONAL MIGRATIONP01NS039404 · NINDS · UNIVERSITY OF CHICAGO · PI DOBYNS, WILLIAM B · 1999 to 2003
$4.9M
Molecular Characterization of Pontocerebellar HypoplasiaR01NS098004 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JOSEPH G GLEESON · 2016 to 2026
$4.6M
Genes and pathways underlying brain overgrowth and focal cortical malformationsK08NS092898 · NINDS · SEATTLE CHILDREN'S HOSPITAL · PI MIRZAA, GHAYDA · 2015 to 2019
$930k
High Performance Computing Instrumentation for the Yale Center for Genome AnalysiS10OD018521 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2015 to 2015
$890k
HSRD VA CDA 14-422Medical Research Council G0802760Medical Research Council G1001253Medical Research Council G108/638Medical Research Council MR/S01165X/1NHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54 HG006504NHGRI NIH HHS UM1 HG008900NIH HHS S10 OD018521NIMH NIH HHS U01 MH108898NINDS NIH HHS K08 NS092898NINDS NIH HHS P01 NS039404NINDS NIH HHS R01 NS048453NINDS NIH HHS R01 NS098004The Dunhill Medical Trust R605/0717Wellcome TrustWellcome Trust WT093205 MAWellcome Trust WT104033AIA
6 · The paper itself

Abstract

Lissencephaly is a severe brain malformation in which failure of neuronal migration results in agyria or pachygyria and in which the brain surface appears unusually smooth. It is often associated with microcephaly, profound intellectual disability, epilepsy, and impaired motor abilities. Twenty-two genes are associated with lissencephaly, accounting for approximately 80% of disease. Here we report on 12 individuals with a unique form of lissencephaly; these individuals come from eight unrelated families and have bi-allelic mutations in APC2, encoding adenomatous polyposis coli protein 2. Brain imaging studies demonstrate extensive posterior predominant lissencephaly, similar to PAFAH1B1-associated lissencephaly, as well as co-occurrence of subcortical heterotopia posterior to the caudate nuclei, "ribbon-like" heterotopia in the posterior frontal region, and dysplastic in-folding of the mesial occipital cortex. The established role of APC2 in integrating the actin and microtubule cytoskeletons to mediate cellular morphological changes suggests shared function with other lissencephaly-encoded cytoskeletal proteins such as α-N-catenin (CTNNA2) and platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (PAFAH1B1, also known as LIS1). Our findings identify APC2 as a radiographically distinguishable recessive form of lissencephaly.

Indexed as

AllelesClassical Lissencephalies and Subcortical Band HeterotopiasCytoskeletal ProteinsDevelopmental DisabilitiesFemaleHumansLissencephalyMalePedigreeAPC2 protein, humanCytoskeletal ProteinsagyriaAPC2band heterotopiaepilepsyintellectual disabilitylissencephalyneuronal migrationpachygyria

Identifiers

PMID31585108
PMCPMC6817548
OpenAlexW2978183744

What OpenQuestion holds

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Read underepoch 390

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.