A Rare MYH11 Gene Missense Variant in a Patient with Intracerebral Vascular and Ascending Aortic Disease and Clinical Strokes
Rodica E Petrea1, Natasha Y Frank2, Oleksandr Olifir2, Cory D Siegel3, Haley Huggins5, Viken L Babikian4
1Neurology, Touro University Medical Group and Boston VA Healthcare System, 2Genetics, Brigham and Women Hospital, 3Neuroradiology, 4Neurology, Boston VA Healthcare System, 5Neurology, Boston Medical Center
Objective:
- To report a patient with complex brain and arterial pathology associated with a MYH11 gene missense variant.
Background:
Background: The MYH11 gene encodes the myosin heavy chain, a specific contractile protein in the smooth muscle. MYH11 pathogenic variants lead to abnormal smooth muscle contractility in arterial walls. They have been associated with specific phenotypes of thoracic aortic aneurysm and dissection, and only rare cases with cerebral arterial disease and stroke have been reported, mostly in children.
Design/Methods:
- Case Report: A 58-year-old black man was seen after recurrent strokes at age 43, 52, and 55. He had a familial history of stroke and a personal history of hypertension and hyperlipidemia. He developed dementia with aphasia and right hemiparesis after his third clinical stroke.
Results:
- Brain magnetic resonance angiography at age 55 showed 5 outpouchings or small aneurysms arising from the intracranial internal carotid arteries (ICAs), a 7.6x4.6 mm aneurysm of the basilar artery, and severely stenotic lesions of the intracranial ICAs, middle and posterior cerebral arteries bilaterally, as well as the basilar artery. Brain magnetic resonance imaging showed a mixture of small and large artery old infarcts and white matter disease. The descending thoracic aorta was ectatic, and abdominal aorta was aneurysmal. Exome sequencing identified a rare MYH11:c.3818G>T, p.(Arg1273Leu) heterozygous variant.
Conclusions:
- We report a case of a formerly unpublished MYH11:c.3818G>T, p.(Arg1273Leu) variant in a patient with multiple brain infarcts early in life, intracranial arterial aneurysms and arterial stenoses, in addition to aortic anomalies, and familial history of stroke. The MYH11:c.3818G>T, p.(Arg1273Leu) variant is classified as a variant of unknown clinical significance according to American College of Medical Genetics criteria. Further studies are needed to further establish it’s clinical significance.
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