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REDES/FIBHULP08. FIBHULP PI: 2735. FIBHULP Auchan Reserch Project. FIBHULP. Raregenomics (B2017/BMD-3721). Referencias bibliográficas: • Anderlid B.-M. Schoumans J. Annerén G. Sahlén S. Kyllerman M. Vujic M. et al. (2002a). Subtelomeric Rearrangements Detected in Patients with Idiopathic Mental Retardation. Am. J. Med. Genet. 107 (4), 275–284. 10.1002/ajmg.10029 • Anderlid B.-M. Schoumans J. Annerén G. Tapia-Paez I. Dumanski J. Blennow E. et al. (2002b). FISH-mapping of a 100-kb Terminal 22q13 Deletion. Hum. Genet. 110 (5), 439–443. 10.1007/s00439-002-0713-7 • Betancur C. Buxbaum J. D. (2013). SHANK3 Haploinsufficiency: a "common" but Underdiagnosed Highly Penetrant Monogenic Cause of Autism Spectrum Disorders. Mol. Autism 4 (1), 17. 10.1186/2040-2392-4-17 • Boccuto L. Lauri M. Sarasua S. M. Skinner C. D. Buccella D. Dwivedi A. et al. (2013). Prevalence of SHANK3 Variants in Patients with Different Subtypes of Autism Spectrum Disorders. Eur. J. Hum. Genet. 21, 310–316. 10.1038/ejhg.2012.175 • Boeckers T. M. (2006). The Postsynaptic Density. Cell Tissue Res 326 (2), 409–422. 10.1007/s00441-006-0274-5 • Bonaglia M. C. Giorda R. Beri S. De Agostini C. Novara F. Fichera M. et al. (2011). Molecular Mechanisms Generating and Stabilizing Terminal 22q13 Deletions in 44 Subjects with Phelan/McDermid Syndrome. Plos Genet. 7, e1002173. 10.1371/journal.pgen.1002173 • Bonaglia M. C. Giorda R. Borgatti R. Felisari G. Gagliardi C. Selicorni A. et al. (2001b). Disruption of the ProSAP2 Gene in a t(12;22)(q24.1;q13.3) Is Associated with the 22q13.3 Deletion Syndrome. Am. J. Hum. Genet. 69 (2), 261–268. 10.1086/321293 • Bonaglia M. C. Giorda R. Mani E. Aceti G. Anderld B. M. Baroncini A. et al. (2001a). Identification of a Recurrent Breakpoint within the SHANK3 Gene in the 22q13.3 Deletion Syndrome. Am. J. Hum. Genet. 69 (2), 261–268. • Bowling K. M. Thompson M. L. Amaral M. D. Finnila C. R. Hiatt S. M. Engel K. L. et al. (2017). Genomic Diagnosis for Children with Intellectual Disab, Phelan-McDermid syndrome (PMS, OMIM# 606232) results from either different rearrangements at the distal region of the long arm of chromosome 22 (22q13.3) or pathogenic sequence variants in the SHANK3 gene. SHANK3 codes for a structural protein that plays a central role in the formation of the postsynaptic terminals and the maintenance of synaptic structures. Clinically, patients with PMS often present with global developmental delay, absent or severely delayed speech, neonatal hypotonia, minor dysmorphic features, and autism spectrum disorders (ASD), among other findings. Here, we describe a cohort of 210 patients with genetically confirmed PMS. We observed multiple variant types, including a significant number of small deletions (<0.5 Mb, 64/189) and SHANK3 sequence variants (21 cases). We also detected multiple types of rearrangements among microdeletion cases, including a significant number with post-zygotic mosaicism (9.0%, 17/189), ring chromosome 22 (10.6%, 20/189), unbalanced translocations (de novo or inherited, 6.4%), and additional rearrangements at 22q13 (6.3%, 12/189) as well as other copy number variations in other chromosomes, unrelated to 22q deletions (14.8%, 28/189). We compared the clinical and genetic characteristics among patients with different sizes of deletions and with SHANK3 variants. Our findings suggest that SHANK3 plays an important role in this syndrome but is probably not uniquely responsible for all the spectrum features in PMS. We emphasize that only an adequate combination of different molecular and cytogenetic approaches allows an accurate genetic diagnosis in PMS patients. Thus, a diagnostic algorithm is proposed., Depto. de Investigación y Psicología en Educación, Fac. de Educación, TRUE, pub