Novel mutation in ENG causes autosomal dominant isolated cerebral arteriovenous malformation at
young age

Background/Objectives:
Cerebral arteriovenous malformation (CAVM) constitute abnormal vessels shunting blood from the
arterial to the venous circulation, resulting in high flow lesions prone to rupture. CAVMs account for
~2% of all hemorrhagic strokes. Most CAVM cases are sporadic, although few are due to autosomal
dominant inheritance of a genetic mutation, most commonly in the context of Hereditary
Hemorrhagic Telangiectasia (HHT), an autosomal dominant genetic disorder characterized by
epistaxis, telangiectasias, and multiorgan vascular dysplasia. We studied a case of father and
daughter with isolated CAVM ruptures at young age, aiming to identify mutations that cause CAVM.

Methods:
Magnetic resonance angiography, whole exome sequencing and validation through PCR and Sanger
sequencing

Results:
A father and daughter presented with isolated CAVM, with ruptures at an early age. Both were
examined clinically and did not present telangiectasias. A frameshift mutation in ENG (endoglin)
chr9:127816006 AG>A HET. (hg38) was found in both affected father and daughter.

Conclusion:
Mutations in ENG have been reported to cause HHT1, a subtype of HHT with higher risk for
developing CAVM than other subtypes of the disease. This new mutation is unique in causing CAVM
at a very young age and without skin presentation of telangiectasias. Thus, genetic testing is
important for diagnosis of HHT in families with history of isolated CAVM ruptures.

References:
1) C. Stapf et. al. (2002). Incidence of adult brain arteriovenous malformation hemorrhage in
a prospective population-based stroke survey. Cerebrovascular Diseases
2) Abdalla, S. A., & Letarte, M. (2006). Hereditary haemorrhagic telangiectasia: Current
views on genetics and mechanisms of disease. Journal of Medical Genetics

Grants:

The Morris Kahn foundation