A. K. Bednarek, K. J. Laflin, R. L. Daniel, Q. Liao, K. A. Hawkins et al., WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3-24.1, a region frequently affected in breast cancer, Cancer Res, vol.60, pp.2140-2145, 2000.

S. White, J. Hewitt, and E. Turbitt, A multi-exon deletion within WWOX is associated with a 46,XY disorder of sex development, Eur J Hum Genet, vol.20, pp.348-351, 2012.

M. Mallaret, M. Synofzik, and J. Lee, The tumour suppressor gene WWOX is mutated in autosomal recessive cerebellar ataxia with epilepsy and mental retardation, Brain, vol.137, pp.411-419, 2014.

A. Thoenes, M. Afifi, H. H. Korber, F. Swan, D. Bolz et al., The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration, Orphanet J Rare Dis, vol.9, pp.1172-1181, 2014.

C. Mignot, L. Lambert, and L. Pasquier, WWOX-related encephalopathies: delineation of the phenotypical spectrum and emerging genotypephenotype correlation, J Med Genet, vol.52, pp.61-70, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01686391

S. Ben-salem, A. -. Shamsi, A. M. John, A. Ali, B. R. Al-gazali et al., A novel whole exon deletion in WWOX gene causes early epilepsy, intellectual disability and optic atrophy, J Mol Neurosci, vol.56, pp.17-23, 2015.

M. Valduga, C. Philippe, and L. Lambert, WWOX and severe autosomal recessive epileptic encephalopathy: first case in the prenatal period, J Hum Genet, vol.60, pp.267-271, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01686358

B. Tabarki, A. Alhashem, S. Alshahwan, F. S. Alkuraya, S. Gedela et al., Severe CNS involvement in WWOX mutations: description of five new cases, Am J Med Genet A, vol.167, pp.3209-3213, 2015.

A. M. Alkhateeb, S. K. Aburahma, W. Habbab, and I. R. Thompson, Novel mutations in WWOX, RARS2, and C10orf2 genes in consanguineous Arab families with intellectual disability, Metab Brain Dis, vol.31, pp.901-907, 2016.

D. R. Zerbino, P. Achuthan, and W. Akanni, Nucleic Acids Res, vol.46, issue.D1, pp.754-61, 2018.

C. Bonnet, B. Leheup, M. Beri, C. Philippe, M. J. Gregoire et al., Aberrant GRIA3 transcripts with multi-exon duplications in a family with X-linked mental retardation, Am J Med Genet A, vol.149, pp.1280-1289, 2009.

V. Carmignac, J. Thevenon, and L. Ades, In-frame mutations in exon 1 of SKI cause dominant Shprintzen-Goldberg syndrome, 13. SeattleSeq Annotation, vol.91, pp.950-957, 2012.
URL : https://hal.archives-ouvertes.fr/hal-01670135

J. T. Robinson, H. Thorvaldsdottir, and W. Winckler, Integrative Genomics Viewer. Nat Biotechnol, vol.29, pp.24-26, 2011.

K. Chen, J. W. Wallis, and M. D. Mclellan, BreakDancer: an algorithm for high-resolution mapping of genomic structural variation, Nat Methods, vol.6, pp.677-681, 2009.

R. Xi, A. G. Hadjipanayis, and L. J. Luquette, Copy number variation detection in whole-genome sequencing data using the Bayesian information criterion, Proc Natl Acad Sci USA, vol.108, issue.46, pp.1128-1136, 2011.

A. Quenard, S. Yilmaz, and H. Fontaine, Deleterious mutations in exon 1 of MECP2 in Rett syndrome, Eur J Med Genet, vol.49, pp.313-322, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00655311

, Genome Reference Consortium, 2009.

, Human Genome Variation Society, 2016.

M. Lek, K. J. Karczewski, and E. V. Minikel, Analysis of protein-coding genetic variation in 60,706 humans, Nature, vol.536, pp.285-291, 2016.

M. I. Nunez, J. Ludes-meyers, and C. M. Aldaz, WWOX protein expression in normal human tissues, J Mol Histol, vol.37, pp.115-125, 2006.

R. I. Aqeilan, F. Trapasso, and S. Hussain, Targeted deletion of Wwox reveals a tumor suppressor function, Proc Natl Acad Sci USA, vol.104, pp.3949-3954, 2007.

N. S. Chang, L. J. Hsu, Y. S. Lin, F. J. Lai, and H. M. Sheu, WW domain-containing oxidoreductase: a candidate tumor suppressor, Trends Mol Med, vol.13, pp.12-22, 2007.

N. S. Chang, N. Pratt, and J. Heath, Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity, J Biol Chem, vol.276, pp.3361-3370, 2001.

J. R. Macdonald, R. Ziman, R. K. Yuen, L. Feuk, and S. W. Scherer, The Database of Genomic Variants: a curated collection of structural variation in the human genome, Nucleic Acids Res, vol.42, pp.986-92, 2014.

S. T. Chen, J. I. Chuang, J. P. Wang, M. S. Tsai, H. Li et al., Expression of WW domain-containing oxidoreductase WOX1 in the developing murine nervous system, Neuroscience, vol.124, pp.831-839, 2004.

H. Suzuki, K. Katayama, M. Takenaka, K. Amakasu, K. Saito et al., A spontaneous mutation of the Wwox gene and audiogenic seizures in rats with lethal dwarfism and epilepsy, Genes Brain Behav, vol.8, pp.650-660, 2009.

C. M. Aldaz, B. W. Ferguson, and M. C. Abba, WWOX at the crossroads of cancer, metabolic syndrome related traits and CNS pathologies, Biochim Biophys Acta, vol.1846, pp.188-200, 2014.

M. Gribaa, M. Salih, and M. Anheim, A new form of childhood onset, autosomal recessive spinocerebellar ataxia and epilepsy is localized at 16q21-q23, Brain, vol.130, pp.1921-1928, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00189388

L. Elsaadany, M. El-said, A. R. Kamel, H. Ben-omran, and T. , W44X mutation in the WWOX gene causes intractable seizures and developmental delay: a case report, BMC Med Genet, vol.17, p.53, 2016.

S. Richards, N. Aziz, and S. Bale, Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, Genet Med, vol.17, pp.405-424, 2015.

D. Sandre-giovannoli, A. Bernard, R. Cau, and P. , Lamin a truncation in Hutchinson-Gilford progeria, Science, vol.300, p.2055, 2003.

H. Wu, A. Boulling, and D. N. Cooper, Analysis of the impact of known SPINK1 missense variants on pre-mRNA splicing and/or mRNA stability in a full-length gene assay, Genes (Basel), vol.8, 2017.

J. H. Ludes-meyers, H. Kil, and M. I. Nunez, WWOX hypomorphic mice display a higher incidence of B-cell lymphomas and develop testicular atrophy, Genes Chromosomes Cancer, vol.46, pp.1129-1136, 2007.

L. Yang, B. Liu, and B. Huang, A functional copy number variation in the WWOX gene is associated with lung cancer risk in Chinese, Hum Mol Genet, vol.22, pp.1886-1894, 2013.

L. Yang, F. Qiu, and W. Fang, The functional copy number variation-67048 in WWOX contributes to increased risk of COPD in southern and eastern Chinese, COPD, vol.12, pp.494-501, 2015.

Y. Chen, X. Tan, and Y. Ding, WWOX CNV-67048 functions as a risk factor for epithelial ovarian cancer in Chinese women by negatively interacting with oral contraceptive use, Biomed Res Int, p.6594039, 2016.

S. Singla, J. Chen, and S. Sethuraman, Loss of lung WWOX expression causes neutrophilic inflammation, Am J Physiol Lung Cell Mol Physiol, vol.312, pp.903-914, 2017.

R. I. Aqeilan, J. P. Hagan, and A. De-bruin, Targeted ablation of the WW domain-containing oxidoreductase tumor suppressor leads to impaired steroidogenesis, Endocrinology, vol.150, pp.1530-1535, 2009.

J. H. Kim, E. Kang, and S. H. Heo, Diagnostic yield of targeted gene panel sequencing to identify the genetic etiology of disorders of sex development, Mol Cell Endocrinol, vol.444, p.25, 2017.

G. Centre-de and . Humaine,

O. Centre-for-genomic-medicine, Oxford University Hospitals NHS Foundation Trust

, La Timone Children's Hospital

, La Timone Children's Hospital

. Service-de-génétique, C. Ouest, and . Rennes,

R. Département-de-génétique, . Debré, and . Paris,

D. Aphp and . De-génétique, Centre de Référence Déficiences Intellectuelles de Causes Rares

. Hospitalier-pitié-salpêtrière, S. Trousseau, . Université, and A. Grc-"déficience-intellectuelle,

, ICM, Inserm U1127, CNRS UMR 7225

, Clinical Psychiatry Hospital, Carol Davila" University of Medicine

, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust

, 16 Department of Clinical Genetics, Sheffield Children's NHS Trust, Sheffield, United Kingdom. 17 Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust

, Wellcome Genome Campus

, Clinical Genetics Department

N. Département-de,

I. Montpellier, 22 Department for Clinical Genetics, Erasmus MC, vol.23, p.24, 1051.

. Laboratoire-de-génétique, Innovations en diagnostic génomique des maladies rares