A de novo microdeletion of SEMA5A in a boy with autism spectrum disorder and intellectual disability

作者：Mosca Boidron Anne Laure^*; Gueneau Lucie; Huguet Guillaume; Goldenberg Alice; Henry Celine; Gigot Nadege; Pallesi Pocachard Emilie; Falace Antonio; Duplomb Laurence; Thevenon Julien; Duffourd Yannis; ST Onge Judith; Chambon Pascal; Riviere Jean Baptiste; Thauvin Robinet Christel; Callier Patrick; Marle Nathalie; Payet Muriel; Ragon Clemence; Botros Hany Goubran; Buratti Julien; Calderari Sophie; Dumas Guillaume; Delorme Richard; Lagarde Nathalie; Pinoit Jean Michel

来源：European Journal of Human Genetics, 2016, 24(6): 838-843.

DOI：10.1038/ejhg.2015.211

Semaphorins are a large family of secreted and membrane-associated proteins necessary for wiring of the brain. Semaphorin 5A (SEMA5A) acts as a bifunctional guidance cue, exerting both attractive and inhibitory effects on developing axons. Previous studies have suggested that SEMA5A could be a susceptibility gene for autism spectrum disorders (ASDs). We first identified a de novo translocation t(5; 22)(p15.3; q11.21) in a patient with ASD and intellectual disability (ID). At the translocation breakpoint on chromosome 5, we observed a 861-kb deletion encompassing the end of the SEMA5A gene. We delineated the breakpoint by NGS and observed that no gene was disrupted on chromosome 22. We then used Sanger sequencing to search for deleterious variants affecting SEMA5A in 142 patients with ASD. We also identified two independent heterozygous variants located in a conserved functional domain of the protein. Both variants were maternally inherited and predicted as deleterious. Our genetic screens identified the first case of a de novo SEMA5A microdeletion in a patient with ASD and ID. Although our study alone cannot formally associate SEMA5A with susceptibility to ASD, it provides additional evidence that Semaphorin dysfunction could lead to ASD and ID. Further studies on Semaphorins are warranted to better understand the role of this family of genes in susceptibility to neurodevelopmental disorders.

• 出版日期2016-6