Oasi Research Institute-IRCCS, Troina, Italy.
Department of Biomedical and Biotechnological Sciences, Medical Genetics, University of Catania, Catania, Italy.
Eur J Hum Genet. 2019 Apr;27(4):594-602. doi: 10.1038/s41431-018-0321-1. Epub 2019 Jan 18.
In recent years, chromosomal microarray analysis has permitted the discovery of rearrangements underlying several neurodevelopmental disorders and still represents the first diagnostic test for unexplained neurodevelopmental disabilities. Here we report a family of consanguineous parents showing psychiatric disorders and their two sons both affected by intellectual disability, ataxia, and behavioral disorder. SNP/CGH array analysis in this family demonstrated in both siblings a biallelic duplication inherited from the heterozygous parents, disrupting the ADGRB3 gene. ADGRB3, also known as BAI3, belongs to the subfamily of adhesion G protein-coupled receptors (adhesion GPCRs) that regulate many aspects of the central nervous system, including axon guidance, myelination, and synapse formation. Single nucleotide polymorphisms and copy number variants involving ADGRB3 have recently been associated with psychiatric disorders. These findings further support this association and also suggest that biallelic variants affecting the function of the ADGRB3 gene may also cause cognitive impairments and ataxia.
近年来，染色体微阵列分析已经发现了一些神经发育障碍的基础重排，并且仍然是不明原因的神经发育障碍的第一个诊断测试。在这里，我们报告了一个有亲缘关系的父母患有精神疾病的家庭，他们的两个儿子都患有智力障碍、共济失调和行为障碍。对这个家庭的 SNP/CGH 阵列分析表明，在这对兄弟姐妹中，有一种来自杂合父母的双等位基因重复，破坏了 ADGRB3 基因。ADGRB3，也称为 BAI3，属于粘附 G 蛋白偶联受体（adhesion GPCRs）的亚家族，调节中枢神经系统的许多方面，包括轴突导向、髓鞘形成和突触形成。涉及 ADGRB3 的单核苷酸多态性和拷贝数变异最近与精神疾病有关。这些发现进一步支持了这种关联，并表明影响 ADGRB3 基因功能的双等位基因变异也可能导致认知障碍和共济失调。
