Abstract
Autism spectrum disorder (ASD) is a set of neurodevelopmental conditions characterized by early-onset difficulties in social communication and unusually restricted, repetitive behavior and interests. Parental consanguinity may lead to higher risk of ASD and to more severe clinical presentations in the offspring. Studies of ASD families with high inbreeding enable the identification of inherited variants of this disorder particularly those with an autosomal recessive pattern of inheritance. In our study, using copy number variants (CNV) analysis, we identified a rare homozygous deletion in 2p11.2 region that affects ELMOD3, CAPG, and SH2D6 genes in a boy with ASD, intellectual disability (ID), and hearing impairment (HI). This deletion may reveal a new contiguous deletion syndrome in which ELMOD3, known to be implicated in autosomal recessive deafness underlies the HI of the proband and CAPG, member of actin regulatory proteins involved in cytoskeletal dynamic, an important function for brain development and activity, underlies the ASD/ID phenotype. A possible contribution of SH2D6 gene, as a part of a chimeric gene, to the clinical presentation of the patient is discussed. Our result supports the implication of ELMOD3 in hearing loss and highlights the potential clinical relevance of 2p11.2 deletion in autism and/or intellectual disability.
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Acknowledgments
We are grateful to the patient and his family for their participation in the study.
Author contribution statement
SL performed the experiments and the analysis of the data and wrote the manuscript. CSL and AM analyzed the data. MH, IBY, AB, and IK contributed through clinical investigation of the patient. CSL and HJ contributed through discussions and revised the manuscript. BR, LL, and RM performed the experiments. SA and TB reviewed the manuscript and supervised the study.
Funding
This work was supported by the Tunisian Ministry of Public Health, the Ministry of Higher Education and Scientific Research (LR16IPT05), and the Institut Pasteur, the University Paris Diderot and the CNRS.
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This study was conducted according to the principles of the declaration of Helsinki. The ethics approval (2016/17/I/LR11IPT05) was obtained from the institutional review board of Pasteur Institute (Tunis- Tunisia- Registration number IRB00005445, FWA00010074).
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The authors declare that they have no conflict of interest.
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Written informed consent was obtained from the family members or their guardians for being included in the study.
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Communicated by: Michal Witt
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Lahbib, S., Leblond, C.S., Hamza, M. et al. Homozygous 2p11.2 deletion supports the implication of ELMOD3 in hearing loss and reveals the potential association of CAPG with ASD/ID etiology. J Appl Genetics 60, 49–56 (2019). https://doi.org/10.1007/s13353-018-0472-3
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DOI: https://doi.org/10.1007/s13353-018-0472-3