Identification of a Common PROC Gene Mutation in Children with Moyamoya Disease Using Whole Exome Sequencing

N. Sirachainan¹, P. Pongphitcha¹, Y. Okuno², L. Thampratankul¹, C. Khongkhatithum¹, P. Komvilaisak³, T. Tim-Aroon¹, D. Songdej¹, D. Wattanasirichaigoon¹.

¹Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, ²Medical Genomics Center, Nagoya University Hospital, Nagoya, Japan, ³Faculty of Medicine Khon Kaen University, Khon Kaen, Thailand

Abstract Number: PB0813

Meeting: ISTH 2021 Congress

Theme: Pediatrics » Thrombosis in Neonates and Children

Background: Moyamoya is characterized by stenosis of internal carotid artery and compensatory developing collateral vessels. It is more common in Asian countries compared to the Western countries. The incidence is around 2-3:100,000 population per year. There are bimodal distributions: age <10 years and 45-49 years. Moyamoya is classified into moyamoya syndrome and disease. Moyamoya syndrome associates with underlying conditions, such as sickle cell disease, neurofibromatosis type 1, and post-radiation, while moyamoya disease does not. The etiologies causing abnormal vascular formation are unknown; therefore, this study is to report the results of whole exome sequencing (WES) in pediatric patients diagnosed with moyamoya.

Aims: To identify genetic abnormality in children with moyamoya

Methods: Children aged <18 years, diagnosed with moyamoya by MRI/MRA study, were studied. After informed consent, WES was performed by using the SOPHiA DDM^® platform (Sophia Genetics, SA). The demographic data, such as age, gender, treatment, and outcome were recorded.

Results: A total of 11 patients, female: male 1.8:1, median (range) age at diagnosis 8.2 (1.7-12.6) years, were enrolled. Moyamoya disease was diagnosed in seven patients. Moyamoya syndrome consisted of two α-thalassemia, one of each with Williams syndrome and craniopharyngioma post-radiation. The results of WES identified three out of seven patients (42.8%) with moyamoya disease having pathogenic variants as follow; two patients (28.6%) with heterozygous PROC gene mutation (c.565G>T, p.R189W) and one patient (14.3%) with heterozygous RNF213 mutation (c.14429G>A, R4810K). One of the two with heterozygous p.R189W mutation also had homozygous HBB c.79G>A, p.E27K, causing mild anemia. There was no pathogenic variant in patients with moyamoya syndrome.

Conclusions: PROC gene mutation, causing low level of protein C, had shown to be a common pathogenic variant of moyamoya disease in Thai children. The allele frequency of c.565G>T was 0.14, while the reported allele frequency in Thai population was 0.03.

To cite this abstract in AMA style:

Sirachainan N, Pongphitcha P, Okuno Y, Thampratankul L, Khongkhatithum C, Komvilaisak P, Tim-Aroon T, Songdej D, DW. Identification of a Common PROC Gene Mutation in Children with Moyamoya Disease Using Whole Exome Sequencing [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/identification-of-a-common-proc-gene-mutation-in-children-with-moyamoya-disease-using-whole-exome-sequencing/. Accessed December 11, 2023.

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