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Novel interstitial 2q12.3q13 microdeletion predisposes to developmental delay and behavioral problems

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Abstract

Microarray-based comparative genomic hybridization (aCGH) is being increasingly applied to delineate novel genomic disorders and related syndromes in patients with developmental delay. In this study, detailed clinical and cytogenetic data of three unrelated patients with interstitial 2q12.3q13 microdeletion were described and compared with thirteen 2q12.3q13 microdeletion patients, gathered from the medical literature and public databases. 60 K aCGH analysis revealed three overlapping 2q12.3q13 microdeletions measuring 1.88 Mb in patient 1, 1.25 Mb in patient 2, and 0.41 Mb in patient 3, respectively. Confirmation and segregation studies were performed using fluorescence in situ hybridization (FISH) and quantitative real-time PCR. Variable clinical features of 2q12.3q13 microdeletion including microcephaly, prenatal growth retardation, developmental delay, short stature, behavioral problems, learning difficulties, skeletal anomalies, congenital heart defects, and features of ectodermal dysplasia were observed. The boundaries and sizes of the 2q12.3q13 deletions in the sixteen patients were different, but an overlapping region of 249 kb in 2q12.3 was defined. The SRO (smallest region of overlap) encompasses four genes, including LIMS1, RANBP2, CCDC138, and EDAR. Among these genes, RANBP2 is a strong candidate gene for neurological phenotype and genetic susceptibility to viral infections. To our knowledge, this is the first published report of 2q12.3q13 microdeletion syndrome and our observations strongly suggest that these recurrent CNVs may be a novel risk factor for developmental delay with variable expressivity and incomplete penetrance.

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Acknowledgements

We thank to the patients and their families for their kind cooperation.

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Authors and Affiliations

  1. Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes, 9 quai Moncousu, 44093, Nantes cedex 1, France

    Minh-Tuan Huynh, Olivier Pichon, Leila Ghesh, Khalid Alfallaj, Stéphane Bézieau & Claire Bénéteau

  2. Service de Génétique Médicale, Centre Hospitalier Universitaire de Caen, Caen, France

    Marion Gérard & Kara Ranguin

  3. Service D’anatomie Et Cytologie Pathologiques, Centre Hospitalier Universitaire de Nantes, Nantes, France

    Madeleine Joubert

  4. Université de Nantes, CNRS, INSERM, L’institut du Thorax, 44000, Nantes, France

    Stéphane Bézieau

Authors
  1. Minh-Tuan Huynh
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  2. Marion Gérard
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  3. Kara Ranguin
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  4. Olivier Pichon
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  6. Khalid Alfallaj
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  8. Stéphane Bézieau
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  9. Claire Bénéteau
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Correspondence to Minh-Tuan Huynh.

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Clinical information was obtained for patients 1, 2, and 3 following informed consent under a protocol approved by Nantes University Hospital.

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Informed consent for medical photographs was obtained for patients 1 and 3.

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Huynh, MT., Gérard, M., Ranguin, K. et al. Novel interstitial 2q12.3q13 microdeletion predisposes to developmental delay and behavioral problems. Neurogenetics 22, 195–206 (2021). https://doi.org/10.1007/s10048-021-00653-6

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  • DOI: https://doi.org/10.1007/s10048-021-00653-6

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