Association of Somatic GNAQ Mutation With Capillary Malformations in a Case of Choroidal Hemangioma

@article{Bichsel2019AssociationOS,
  title={Association of Somatic GNAQ Mutation With Capillary Malformations in a Case of Choroidal Hemangioma},
  author={Colette Bichsel and Jeremy A. Goss and Mohammed H. Alomari and Sanda Alexandrescu and Richard M. Robb and Lois E. H. Smith and Marcelo L Hochman and Arin K Greene and Joyce Bischoff},
  journal={JAMA Ophthalmology},
  year={2019},
  volume={137},
  pages={91–95}
}
Importance Choroidal hemangiomas are defined by a thickened choroid owing to vessel overgrowth, which may increase the intraocular pressure and lead to glaucoma. Choroidal hemangioma and glaucoma often co-occur in patients with Sturge-Weber syndrome, a rare neurocutaneous disorder characterized by capillary malformations. Objective To determine whether the mutation found in most capillary malformations, GNAQ R183Q (c.548G>A), was present in the choroidal hemangioma of a patient with Sturge… 

Figures from this paper

GNAQ Q209R Mutations Are Highly Specific for Circumscribed Choroidal Hemangioma
TLDR
It appears that the GNAQ mutation spectrum in this tumor is narrow, possibly restricted to p.Q209R, and the spectrum is distinct from that of uveal melanoma, in which alterations resulting in p.
Current concepts on diffuse choroidal hemangioma in Sturge Weber syndrome
TLDR
Management of symptomatic DCH is generally difficult and results in poor visual outcome, thus, treatment is generally unwarranted, unless the hemangioma complicated by serous retinal detachment, and lifelong surveillance is essential in patients.
Progressive retinal vessel malformation in a premature infant with Sturge-Weber syndrome: a case report and a literature review of ocular manifestations in Sturge-Weber syndrome
TLDR
This is a rare case of documented progression of retinal vessel malformations in a patient with Sturge-Weber syndrome and retinopathy of prematurity, after treatment with intravitreal anti-vascular endothelial growth factor (VEGF).
A novel somatic mutation in GNAQ in a capillary malformation provides insight into molecular pathogenesis.
TLDR
RNA-seq analysis in microvascular endothelial cells (HMEC-1) electroporated with the same GNAQ variants confirmed that the R183 and Q209 missense variants caused extensive dysregulation of a broad range of transcripts compared to the WT or null allele, however, the missesense variants exhibited very few differentially expressed genes (DEGs) when compared to each other.
A somatic missense mutation in GNAQ causes capillary malformation
TLDR
Several studies confirm the GNAQ R183Q mutation in 90% of nonsyndromic and Sturge–Weber syndrome (SWS) capillary malformations and insights from computational analyses shed light on the mechanisms of constitutive activation and new basic science shows G&agr;q plays roles in sensing shear stress and in regulating cerebral blood flow.
Somatic GNAQ R183Q mutation is located within the sclera and episclera in patients with Sturge-Weber syndrome
TLDR
This study suggests GNAQ R183Q may regulate episcleral vessels of patients with Sturge-Weber syndrome through abnormal activation of ERK and JNK, providing new genetic evidence of pathogenesis of glaucoma in SWS, and the dysplasia of scleral tissue in anterior segment may be used as an early diagnostic method or treatment targets to prevent the development and progression in patients with SWS.
Encephalotrigeminal Angiomatosis: A Review with Emphasis on Head and Neck Manifestations
TLDR
Common clinical and various imaging manifestations of Sturge-Weber syndrome, including head and neck and intracranial imaging findings, are recognized, including involvement of the extraocular muscles, salivary glands, and lacrimal glands.
Incidence of Sturge–Weber syndrome and associated ocular involvement in Olmsted County, Minnesota, United States
TLDR
Early diagnosis, intervention, lifelong follow-up, and multidisciplinary approach should be used to optimize systemic and ocular outcomes in Sturge–Weber syndrome.
...
...

References

SHOWING 1-10 OF 15 REFERENCES
Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ.
TLDR
The Sturge-Weber syndrome and port-wine stains are caused by a somatic activating mutation in GNAQ, and this finding confirms a long-standing hypothesis.
Endothelial Cells from Capillary Malformations Are Enriched for Somatic GNAQ Mutations
TLDR
Endothelial cells in capillary malformations are enriched for GNAQ mutations and are likely responsible for the pathophysiology underlying capillarymalformation.
The somatic GNAQ mutation c.548G>A (p.R183Q) is consistently found in Sturge–Weber syndrome
TLDR
It is suggested that the recurrent somatic GNAQ mutation c.548G>A is the major determinant genetic factor for SWS and imply that other mutated candidate gene(s) may exist in SWS.
Ocular manifestations of Sturge–Weber syndrome: pathogenesis, diagnosis, and management
TLDR
The management of glaucoma in Sturge–Weber syndrome patients is particularly challenging because of early onset, frequently associated severe visual field impairment at the time of diagnosis, and unresponsiveness to standard treatment.
The ocular manifestations of the Sturge-Weber syndrome.
TLDR
The authors reviewed the records of and recalled for examination 51 consecutive patients with a diagnosis of Sturge-Weber syndrome seen at The Hospital for Sick Children, Toronto, Ontario, Canada, from 1980 to 1991, finding thirty-four of 51 glaucomatous eyes had a final visual acuity of 20/40 or better, or central, steady, and maintained fixation in each eye.
Sturge‐Weber Syndrome in Patients with Facial Port‐Wine Stain
TLDR
Knowledge of the topography of facial PWS with risk of associated neurological or ocular anomalies allows for early diagnosis of SWS and avoids unnecessary and costly radiography for patients with uncomplicated facial P WS.
Failure of systemic propranolol therapy for choroidal hemangioma of Sturge-Weber syndrome: a report of 2 cases.
TLDR
The outcome of oral propranolol therapy in 2 cases with choroidal hemangioma of SturgeWeber syndrome (SWS) is reported.
...
...