Evidence map›Paper›PMID 25356967›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2015

Consanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCD.

Peter J Shepard, Bruce A Barshop, Matthias R Baumgartner, John-Bjarne Hansen, Kristen Jepsen, Erin N Smith, Kelly A Frazer

Open 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, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.3field-weighted citation impact, top 22% 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

5 citing papers in PubMed, 15 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

7 authors at 3 institutions in 3 countries.

Peter J ShepardDepartment of Pediatrics, Rady Children's Hospital, University of California, San Diego, La Jolla, California, USA.
Bruce A Barshop1] Department of Pediatrics, Rady Children's Hospital, University of California, San Diego, La Jolla, California, USA [2] Clinical and Translational Research Institute, University of California, San Diego, La Jolla, California, USA.
Matthias R Baumgartner1] Division of Metabolic Diseases and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland [2] Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.ORCID 0000000292700826
John-Bjarne HansenDepartment of Clinical Medicine, University of Tromsø, Tromsø, Norway.
Kristen Jepsen1] Department of Pediatrics, Rady Children's Hospital, University of California, San Diego, La Jolla, California, USA [2] Clinical and Translational Research Institute, University of California, San Diego, La Jolla, California, USA.
Erin N Smith1] Department of Pediatrics, Rady Children's Hospital, University of California, San Diego, La Jolla, California, USA [2] Clinical and Translational Research Institute, University of California, San Diego, La Jolla, California, USA.
Kelly A Frazer1] Department of Pediatrics, Rady Children's Hospital, University of California, San Diego, La Jolla, California, USA [2] Clinical and Translational Research Institute, University of California, San Diego, La Jolla, California, USA [3] Institute for Genomic Medicine, University of California, San Diego, La Jolla, California, USA.
University of California San Diego · USUiT The Arctic University of Norway · NOUniversity of Zurich · CH

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
UCSD Cancer Center Training Program in Drug DevelopmentT32CA121938 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Bouvet, Dwayne G. Stupack · 2006 to 2026
$10.3M
Genetic Factors Involving Expression of 3-Methylcrotonyl-CoA Carboxylase DeficienR03HD069983 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BARSHOP, BRUCE A · 2011 to 2012
$155k
NCI NIH HHS P30 CA023100NCI NIH HHS T32 CA121938NICHD NIH HHS 5R03HD69983-2NICHD NIH HHS R03 HD069983
6 · The paper itself

Abstract

purpose3-Methylcrotonyl-CoA carboxylase deficiency (MCCD) is an autosomal recessive disorder of leucine catabolism that has a highly variable clinical phenotype, ranging from acute metabolic acidosis to nonspecific symptoms such as developmental delay, failure to thrive, hemiparesis, muscular hypotonia, and multiple sclerosis. Implementation of newborn screening for MCCD has resulted in broadening the range of phenotypic expression to include asymptomatic adults. The purpose of this study was to identify factors underlying the varying phenotypes of MCCD.

methodsWe performed exome sequencing on DNA from 33 cases and 108 healthy controls. We examined these data for associations between either MCC mutational status, genetic ancestry, or consanguinity and the absence or presence/specificity of clinical symptoms in MCCD cases.

resultsWe determined that individuals with nonspecific clinical phenotypes are highly inbred compared with cases that are asymptomatic and healthy controls. For 5 of these 10 individuals, we discovered a homozygous damaging mutation in a disease gene that is likely to underlie their nonspecific clinical phenotypes previously attributed to MCCD.

conclusionOur study shows that nonspecific phenotypes attributed to MCCD are associated with consanguinity and are likely not due to mutations in the MCC enzyme but result from rare homozygous mutations in other disease genes.Genet Med 17 8, 660-667.

Indexed as

ConsanguinityAdultAllelesCarbon-Carbon LigasesCase-Control StudiesExomeFemaleGenetic Association StudiesHomozygoteHumansInfant, NewbornMaleMutationNeonatal ScreeningUrea Cycle Disorders, InbornCarbon-Carbon Ligasesmethylcrotonoyl-CoA carboxylase

Identifiers

PMID25356967
PMCPMC4422778
OpenAlexW2017661128

What OpenQuestion holds

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LicenceCC BY
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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.