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

doi:10.1038/s41431-022-01139-1

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

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A novel HRAS c.466C>T p.(Phe156Leu) variant in two patients with attenuated features of Costello syndrome. / Lindsey-Temple, Suzanna; Edwards, Matt; Rickassel, Verena; Nauth, Theresa ; Rosenberger, Georg.

in: EUR J HUM GENET, Jahrgang 30, Nr. 9, 09.2022, S. 1088-1093.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Lindsey-Temple, S, Edwards, M, Rickassel, V, Nauth, T & Rosenberger, G 2022, 'A novel HRAS c.466C>T p.(Phe156Leu) variant in two patients with attenuated features of Costello syndrome', EUR J HUM GENET, Jg. 30, Nr. 9, S. 1088-1093. https://doi.org/10.1038/s41431-022-01139-1

APA

Lindsey-Temple, S., Edwards, M., Rickassel, V., Nauth, T., & Rosenberger, G. (2022). A novel HRAS c.466C>T p.(Phe156Leu) variant in two patients with attenuated features of Costello syndrome. EUR J HUM GENET, 30(9), 1088-1093. https://doi.org/10.1038/s41431-022-01139-1

Vancouver

Lindsey-Temple S, Edwards M, Rickassel V, Nauth T , Rosenberger G. A novel HRAS c.466C>T p.(Phe156Leu) variant in two patients with attenuated features of Costello syndrome. EUR J HUM GENET. 2022 Sep;30(9):1088-1093. https://doi.org/10.1038/s41431-022-01139-1

Bibtex

@article{ee1f659e1b46470881436547ce850b63,

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

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 HRASPhe156Leu. Our data further illustrate the molecular and phenotypic variability of CS.",

author = "Suzanna Lindsey-Temple and Matt Edwards and Verena Rickassel and Theresa Nauth and Georg Rosenberger",

note = "{\textcopyright} 2022. The Author(s).",

year = "2022",

month = sep,

doi = "10.1038/s41431-022-01139-1",

language = "English",

volume = "30",

pages = "1088--1093",

journal = "EUR J HUM GENET",

issn = "1018-4813",

publisher = "NATURE PUBLISHING GROUP",

number = "9",

}

RIS

TY - JOUR

T1 - A novel HRAS c.466C>T p.(Phe156Leu) variant in two patients with attenuated features of Costello syndrome

AU - Lindsey-Temple, Suzanna

AU - Edwards, Matt

AU - Rickassel, Verena

AU - Nauth, Theresa

AU - Rosenberger, Georg

PY - 2022/9

Y1 - 2022/9

N2 - 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 HRASPhe156Leu. Our data further illustrate the molecular and phenotypic variability of CS.

AB - 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 HRASPhe156Leu. Our data further illustrate the molecular and phenotypic variability of CS.

U2 - 10.1038/s41431-022-01139-1

DO - 10.1038/s41431-022-01139-1

M3 - SCORING: Journal article

C2 - 35764878

VL - 30

SP - 1088

EP - 1093

JO - EUR J HUM GENET

JF - EUR J HUM GENET

SN - 1018-4813

IS - 9

ER -