Klippel–Trenaunay and Sturge–Weber Overlap Syndrome with KRAS and GNAQ mutations

He, Rong; Liao, Songjie; Yao, Xiao-li; Huang, Ruxun; Zhang, Jian; Yu, Jian

doi:10.1002/acn3.51106

Cited by 6 publications

(3 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GNAQ mutations are found in a variety of diseases, including but not limited to: p.T96S NK/T cell lymphoma and diffuse bone and soft tissue angiomatosis ( Li et al, 2019 ; Gaeta et al, 2020 ); p.R183Q Klippel-Trenaunay syndrome ( He et al, 2020 ); p.V179M and p.F335L dark skin point mutations and hyperpigmentation ( Garcia et al, 2008 ; Van Raamsdonk et al, 2009 ; Jain et al, 2020 ); p.Q209L or silencing mutations in non-small cell lung cancers ( Choi et al, 2020 ); p.D663fs insertion and p.R385* nonsense mutations in melanocytoma ( Francis et al, 2016 ); p.Q209L and p.Q209P intramedullary and leptomeningeal melanomas ( Fortin Ensign et al, 2020 ); p.S12fs*49 breast cancer ( Schrader et al, 2016 ); and decreased GNAQ expression in brain aging and neurodegeneration ( Wettschureck et al, 2005 ; Frederick et al, 2012 ; Chen et al, 2017 ; Arey et al, 2018 ; Zhai et al, 2019 ; Sun et al, 2020 ). The following diseases discussed in more detail were selected due to the possible overlap in pathogenesis or molecular interactions, with the goal of spurring synergistic research encompassing these conditions and SWS.…”

Section: Overlap With Other Vascular Malformationsmentioning

confidence: 99%

GNAQ mutations drive port wine birthmark-associated Sturge-Weber syndrome: A review of pathobiology, therapies, and current models

Trigt

Kelly

Hughes

2022

Front. Hum. Neurosci.

View full text Add to dashboard Cite

Port-wine birthmarks (PWBs) are caused by somatic, mosaic mutations in the G protein guanine nucleotide binding protein alpha subunit q (GNAQ) and are characterized by the formation of dilated, dysfunctional blood vessels in the dermis, eyes, and/or brain. Cutaneous PWBs can be treated by current dermatologic therapy, like laser intervention, to lighten the lesions and diminish nodules that occur in the lesion. Involvement of the eyes and/or brain can result in serious complications and this variation is termed Sturge-Weber syndrome (SWS). Some of the biggest hurdles preventing development of new therapeutics are unanswered questions regarding disease biology and lack of models for drug screening. In this review, we discuss the current understanding of GNAQ signaling, the standard of care for patients, overlap with other GNAQ-associated or phenotypically similar diseases, as well as deficiencies in current in vivo and in vitro vascular malformation models.

show abstract

Section: Overlap With Other Vascular Malformationsmentioning

confidence: 99%

GNAQ mutations drive port wine birthmark-associated Sturge-Weber syndrome: A review of pathobiology, therapies, and current models

Trigt

Kelly

Hughes

2022

Front. Hum. Neurosci.

View full text Add to dashboard Cite

show abstract

“…However, most studies on large case series were performed in countries different from China [24][25][26]. Only a limited number of vascular malformations with a definitive pathogenic mutation were previously reported in Chinese population [27][28][29]. There is a lack of study describing the somatic mutation spectrum in a large cohort of Chinese patients.…”

Section: Introductionmentioning

confidence: 99%

Somatic mutation spectrum of a Chinese cohort of pediatrics with vascular malformations

Zhang,

He,

et al. 2023

Orphanet J Rare Dis

View full text Add to dashboard Cite

Background Somatic mutations of cancer driver genes are found to be responsible for vascular malformations with clinical manifestations ranging from cutaneous birthmarks to life-threatening systemic anomalies. Till now, only a limited number of cases and mutations were reported in Chinese population. The purpose of this study was to describe the somatic mutation spectrum of a cohort of Chinese pediatrics with vascular malformations. Methods Pediatrics diagnosed with various vascular malformations were collected between May 2019 and October 2020 from Beijing Children’s Hospital. Genomic DNA of skin lesion of each patient was extracted and sequenced by whole-exome sequencing to identify pathogenic somatic mutations. Mutations with variant allele frequency less than 5% were validated by ultra-deep sequencing. Results A total of 67 pediatrics (33 males, 34 females, age range: 0.1–14.8 years) were analyzed. Exome sequencing identified somatic mutations of corresponding genes in 53 patients, yielding a molecular diagnosis rate of 79.1%. Among 29 PIK3CA mutations, 17 were well-known hotspot p.E542K, p.E545K and p.H1047R/L. Non-hotspot mutations were prevalent in patients with PIK3CA-related overgrowth spectrum, accounting for 50.0% (11/22) of detected mutations. The hotspot GNAQ p.R183Q and TEK p.L914F mutations were responsible for the majority of port-wine stain/Sturge–Weber syndrome and venous malformation, respectively. In addition, we identified a novel AKT1 p.Q79K mutation in Proteus syndrome and MAP3K3 p.E387D mutation in verrucous venous malformation. Conclusions The somatic mutation spectrum of vascular malformations in Chinese population is similar to that reported in other populations, but non-hotspot PIK3CA mutations may also be prevalent. Molecular diagnosis may help the clinical diagnosis, treatment and management of these pediatric patients with vascular malformations.

show abstract

“…[66][67][68][69][70] When performed, genetic studies demonstrate overlap the GNAQ R183 variant in these patients with clinical overlap. 71,72…”

mentioning

confidence: 99%

Sturge-Weber Syndrome: A Review of Pathophysiology, Genetics, Clinical Features, and Current Management Approache

Sanchez-Espino¹,

Ivars²,

Antoñanzas³

et al. 2023

TACG

View full text Add to dashboard Cite

Sturge-Weber syndrome (SWS) is a congenital, sporadic, and rare neurocutaneous disorder, characterized by the presence of a facial port-wine birthmark (PWB), glaucoma, and neurological manifestations including leptomeningeal angiomatosis and seizures. It is caused by a postzygotic, somatic, gain-of-function variant of the GNAQ gene, and more recently, the GNA11 gene in association with distinctive clinical features. Neuroimaging can help identify and stratify patients at risk for significant complications allowing closer follow-up; although no presymptomatic treatment has been demonstrated to be effective to date, these patients could benefit from early treatment and/or supportive interventions. Choroid plexus (CP) thickness measurements in brain magnetic resonance imaging (MRI) have a high sensitivity and specificity for early and incipient changes in SWS. In contrast, the absence of pathologic findings makes it possible to rule out associated neurological involvement and leads to periodical observation, with new imaging studies only in cases of new clinical signs/symptoms. Periodic ophthalmological examination is also recommended every 3 months during the first year and yearly afterwards to monitor for glaucoma and choroidal hemangiomas. Treatment for SWS depends on the extent and areas that are affected. These include laser surgery for PWB, anticonvulsants in the case of brain involvement, with either seizures or abnormal EEG, and medical treatment or surgery for glaucoma. Sirolimus has been used in a limited number of patients and appears to be a safe and potentially effective treatment for cutaneous and extra-cutaneous features, however controlled clinical studies have not been carried out. Better knowledge of GNAQ/GNA11 molecular pathways will help to develop future targeted treatments.

show abstract

Klippel–Trenaunay and Sturge–Weber Overlap Syndrome with KRAS and GNAQ mutations

Cited by 6 publications

References 13 publications

GNAQ mutations drive port wine birthmark-associated Sturge-Weber syndrome: A review of pathobiology, therapies, and current models

GNAQ mutations drive port wine birthmark-associated Sturge-Weber syndrome: A review of pathobiology, therapies, and current models

Somatic mutation spectrum of a Chinese cohort of pediatrics with vascular malformations

Sturge-Weber Syndrome: A Review of Pathophysiology, Genetics, Clinical Features, and Current Management Approache

Contact Info

Product

Resources

About