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Homozygous 2p11.2 deletion supports the implication of ELMOD3 in hearing loss and reveals the potential association of CAPG with ASD/ID etiology

  • Saida Lahbib
  • Claire S. Leblond
  • Mariem Hamza
  • Béatrice Regnault
  • Laure Lemée
  • Alexandre Mathieu
  • Hager Jaouadi
  • Rahma Mkaouar
  • Ilhem Ben Youssef-Turki
  • Ahlem Belhadj
  • Ichraf Kraoua
  • Thomas Bourgeron
  • Sonia Abdelhak
Human Genetics • Original Paper
  • 30 Downloads

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.

Keywords

CNV homozygous deletion ELMOD3 CAPG Autism Hearing loss 

Notes

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 information

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.

Compliance with ethical standards

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).

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Written informed consent was obtained from the family members or their guardians for being included in the study.

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Copyright information

© Institute of Plant Genetics, Polish Academy of Sciences, Poznan 2018

Authors and Affiliations

  • Saida Lahbib
    • 1
    • 2
  • Claire S. Leblond
    • 3
    • 4
    • 5
  • Mariem Hamza
    • 6
    • 7
  • Béatrice Regnault
    • 8
  • Laure Lemée
    • 8
  • Alexandre Mathieu
    • 3
    • 4
    • 5
  • Hager Jaouadi
    • 1
  • Rahma Mkaouar
    • 1
  • Ilhem Ben Youssef-Turki
    • 6
    • 9
  • Ahlem Belhadj
    • 6
    • 7
  • Ichraf Kraoua
    • 6
    • 9
  • Thomas Bourgeron
    • 3
    • 4
    • 5
  • Sonia Abdelhak
    • 1
  1. 1.Biomedical Genomics and Oncogenetics Laboratory LR16IPT05Université Tunis El Manar, Institut Pasteur de TunisTunisTunisia
  2. 2.University of Tunis El ManarTunisTunisia
  3. 3.Human Genetics and Cognitive Functions UnitInstitut PasteurParisFrance
  4. 4.CNRS UMR3571, Genes, Synapses and CognitionInstitut PasteurParisFrance
  5. 5.Paris Diderot UniversitySorbonne Paris CitéParisFrance
  6. 6.Faculty of Medicine of TunisUniversity of Tunis El ManarTunisTunisia
  7. 7.Child and Adolescent Psychiatry DepartmentMongi Slim HospitalSidi DaoudTunisia
  8. 8.Plateforme de Génotypage des Eucaryotes, Centre d’Innovation et Recherche Technologique (CITECH)Institut PasteurParisFrance
  9. 9.Research Unit UR12 SP24 and Department of Child and Adolescent NeurologyNational Institute Mongi Ben Hmida of NeurologyTunisTunisia

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