Activated leukocyte cell adhesion molecule/cluster of differentiation 166 rs10933819 (G&gt;A) variant is associated with familial intracranial aneurysms

Aitkulova,Akbota; Mukhtarova,Kymbat; Zholdybayeva,Elena; Medetov,Yerkin; Dzhamantayeva,Botagoz; Kassymbek,Kuat; Utupov,Talgat; Akhmetollayev,Ilyas; Akshulakov,Serik; Kulmambetova,Gulmira; Ramankulov,Yerlan

doi:10.3892/br.2022.1548

Activated leukocyte cell adhesion molecule/cluster of differentiation 166 rs10933819 (G>A) variant is associated with familial intracranial aneurysms

Authors:
- Akbota Aitkulova
- Kymbat Mukhtarova
- Elena Zholdybayeva
- Yerkin Medetov
- Botagoz Dzhamantayeva
- Kuat Kassymbek
- Talgat Utupov
- Ilyas Akhmetollayev
- Serik Akshulakov
- Gulmira Kulmambetova
- Yerlan Ramankulov
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Affiliations: National Center for Biotechnology, Nur Sultan 010000, Republic of Kazakhstan, National Center of Neurosurgery, Nazarbayev University, Nur Sultan 010000, Republic of Kazakhstan
Published online on: June 7, 2022 https://doi.org/10.3892/br.2022.1548
Article Number: 65
Copyright: © Aitkulova et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Rupture of intracranial aneurysms (IAs) is the most common cause of subarachnoid hemorrhage (SAH). Currently, there is sufficient evidence to indicate that inflammatory responses contribute to aneurysm rupture. Moreover, the familial occurrence of SAH suggests that genetic factors may be involved in disease susceptibility. In the present study, a clinically proven case of IA in a patient who is a heterozygous mutation carrier of the activated leukocyte cell adhesion molecule (ALCAM)/cluster of differentiation 166 (CD166) gene, is reported. Genomic DNA was extracted from two siblings diagnosed with SAH and other available family members. A variant prioritization strategy that focused on functional prediction, frequency, predicted pathogenicity, and segregation within the family was employed. Sanger sequencing was also performed on the unaffected relatives to assess the segregation of variants within the phenotype. The verified mutations were sequenced in 145 ethnicity‑matched healthy individuals. Based on whole exome sequencing data obtained from three individuals, two of whom were diagnosed with IAs, the single‑nucleotide variant rs10933819 was prioritized in the family. Only one variant, rs10933819 (G>A), in ALCAM co‑segregated with the phenotype, and this mutation was absent in ethnicity‑matched healthy individuals. Collectively, ALCAM c1382 G>A p.Gly229Val was identified, for the first time, as a pathogenic mutation in this IA pedigree.

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