A novel HRAS c.466C>T p.(Phe156Leu) variant in two patients with attenuated features of Costello syndrome.

Suzanna Lindsey-Temple, Matt Edwards, Verena Rickassel, Theresa Nauth, Georg Rosenberger

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In one paragraph

Article in European journal of human genetics : EJHG, 2022. 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

0.5field-weighted citation impact, top 39% 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

1 citing paper in PubMed, 6 citations in OpenAlex.

Guidelines, guidelines everywhere-and still I'm not sure what to do.European journal of human genetics : EJHG · 2022
Article

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

5 authors at 3 institutions in 2 countries.

Suzanna Lindsey-TempleDepartment of Clinical Genetics, Liverpool Hospital, Sydney, NSW, Australia.

Matt EdwardsPaediatrics, School of Medicine, Western Sydney University, Hunter Genetics, Newcastle, NSW, Australia.

Verena RickasselInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Theresa NauthInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Georg RosenbergerInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. rosenberger@uke.de.ORCID 0000-0003-3625-3109

Universität Hamburg · DEHunter Genetics · AULiverpool Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Costello syndrome (CS) is caused by heterozygous HRAS germline mutations. Most patients share the HRAS variant p.Gly12Ser that is associated with a typical, homogeneous phenotype. Rarer pathogenic HRAS variants (e.g., p.Thr56Ile) were identified in individuals with attenuated CS phenotypes. The obvious phenotypical variability reflects different dysfunctional consequences of distinct HRAS variants. We report on two boys with the novel de novo HRAS variant c.466 C > T p.(Phe156Leu). Both had severe feeding difficulties, airway obstruction and developmental delay, which are typical findings in CS. They showed subtle facial and dermatologic features consistent with attenuated CS. They significantly differed in their musculoskeletal, cardiovascular and endocrinologic manifestations underscoring the clinical variability of individuals with identical, in particular rarer pathogenic HRAS variants. Functional studies revealed enhanced effector-binding, increased downstream signaling activation and impaired growth factor-induced signaling dynamics in cells expressing HRAS

Indexed as

Costello SyndromeChildGerm-Line MutationHeterozygoteHumansMalePhenotypeProto-Oncogene Proteins p21(ras)Signal TransductionHRAS protein, humanProto-Oncogene Proteins p21(ras)

Identifiers

PMID35764878

DOI10.1038/s41431-022-01139-1

PMCPMC9437031

OpenAlexW4283703227

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.