Clinical characterization of six patients with 15q13. 2-q13 Clinical characterization of six patients with 15q13.2-q13.3 microdeletion Sander Pajusalu1, Eve Õiglane-Šlik2,3, Inga Talvik2,3, Rita Teek1,2, Olga Žilina1,4, Kati Kuuse1, Tiia Reimand1,2,5, Katrin Õunap1,2 1Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia 2Department of Pediatrics, University of Tartu 3Children’s Clinic, Tartu University Hospital, 4Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu 5Department of Human Biology and Genetics, Institute of Biomedicine, University of Tartu, Tartu, Estonia INTRODUCTION Individuals with 15q13.3 microdeletion may have wide range of clinical manifestations including intellectual disability (ID), speech delay, epilepsy, autism and schizophrenia. Deletion of CHRNA7 gene in this region is causative for the majority of neurodevelopmental phenotypes in the 15q13.3 microdeletion syndrome. Subset of persons with the deletion have no obvious clinical findings at all. OBJECTIVES To characterize patients with typical 15q13.2-q13.3 microdeletions found by chromosomal microarray (CMA) and to estimate the prevalence of the deletion in our cohort of patients tested with CMA due to their clinical indications (cognitive disorders, dysmorphic features). PATIENTS and METHODS During 2009-2012 the chromosomal microarray analysis (CMA) was performed in 1188 individuals due to their clinical indications. In six individuals 15q13.3 microdeletion was detected: all of them had typical ~1.5Mb deletion between BP4 and BP5. Here we present the clinical features of these six patients. RESULTS and DISCUSSION All our patients (aged 4-8 years of age, among them two pairs of sibs) had ID (borderline to severe), speech delay, but no or mild facial dysmorphism and normal growth parameters. Abnormal EEG was found in four out of five tested patients (80%), which is more frequent than previously reported (van Bon 2009). Still, only one boy has severe treatment resistant generalized epilepsy. Positive family history for epilepsy was documented in two families though. Aggressive behaviour is apparent in two of our patients (33%). Testing of family members has shown familial deletions in all but one patient whose father is unreachable for testing. High percentage of familial deletions is consistent with previously published data (van Bon 2009, Ben-Shachar 2009). In our cohort of patients tested with CMA the 15q13.3 microdeletion was detected in 0.5% of all patients. CONCLUSION 15q13.3 microdeletion represents one of the most frequent microdeletion syndromes found by CMA and characterized by cognitive and behavioural disorders, EEG abnormalities, normal growth, absence of characteristic dysmorphic features and high percentage of familial cases. REFERENCES Ben-Shachar S, Lanpher B, German JR et al. Microdeletion 15q13.3: A locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders. J Med Genet 2009: 46 : 382–388. Van Bon BW, Mefford HC, Menten B et al. Further delineation of the 15q13 microdeletion and duplication syndromes: A clinical spectrum varying from non-pathogenic to a severe outcome. J Med Genet 2009: 46: 511–523. Clinical data of the patients in our study group. # Gender Age at diagnosis Growth (Height and OFC) Dysmorphism Intellectual disability Speech delay Autism EEG abnormalities Epilepsy Behavioural problems Brain MRI Familial / de novo 1 Female 6 Normal No Yes (mild) Yes Familial, sister of pt 2 2 Male 8 Familial, brother of pt 1 3 7 Mild De novo? (Father is unreachable for testing) 4 NA Attention deficit-hyperactivity disorder Familial, brother of pt 5 5 Yes (severe) Aggression, auto-aggression Familial, sister of pt 4 Borderline normal Familial, her mother and maternal grandfather carry the same mutation This research was supported by Estonian Science Foundation grant GARLA8175 and by European Social Fund’s Doctoral Studies and Internationalisation Programme DoRa, which is carried out by Foundation Archimedes.