Anna Lengyel1, Eva Pinti1, Henriett Piko2, Eszter Javorszky3, Kalman Tory3, Mariann Tihanyi4, Gyorgy Fekete1, Iren Haltrich1
1 II. Department of Pediatrics, Semmelweis University, Budapest
2 I. Department of Internal Medicine, Semmelweis University, Budapest
3 I. Department of Pediatrics, Semmelweis University, Budapest
4 Department of Genetics, Zala County Hospital, Zalaegerszeg
Introduction: The short arm of chromosome 16 (16p) is enriched for segmental duplications (SDs), which are highly homologous blocks of DNA flanking unique genomic segments. Misalignment of SDs cause recurrent, reciprocal rearrangements mediated by non-allelic homologous recombination. Such copy number variants (CNVs) of 16p present with heterogenous, unspecific phenotypes and are implicated in the etiology of neuropsychiatric features, including intellectual disability, speech disorders and autism spectrum disorders.
Aim: Identifying CNVs on chromosome 16p and performing detailed clinical evaluations of concerned patients, with special emphasis on behavioral symptoms.
Method: Patients referred to genetic counselling with intellectual disability, developmental delay, dysmorphic features and other congenital anomalies were analyzed using array comparative genomic hybridization. Results were confirmed using either fluorescence in situ hybridization or polymerase chain reaction.
Results: Out of 72 individuals, 11 patients had 12 CNVs of chromosome 16p, eight of which corresponded to recurrent CNVs. We identified one deletion and one duplication of 16p12.2. This region is associated with the 16p11.2p12.2 microdeletion/microduplication syndrome and the typical ~500 kb 16p12.2 microdeletion that confers risk for neurodevelopmental disorders. Two patients had deletions partially overlapping the distal, ~220 kb 16p11.2 region where the obesity associated SH2B1 gene is located. Four duplications of the well described autism spectrum disorder “hotspot” region of 16p11.2 were discovered. We found four additional rare, non-recurrent proximal 16p11.2 alterations not yet associated with known disorders: one deletion, one large loss of heterozygosity and two duplications.
Conclusion: We present the phenotypic and genotypic results of our patients and discuss our findings in relation to the available literature. Our results corroborate previous knowledge, bring attention to novel aspects involving the well known CNVs, and introduce three non-recurrent CNVs resulting in comparable clinical consequences.
Doctoral School: Clinical Medicine
Program: Clinical application of basic science results
Supervisor: Iren Haltrich
E-mail address: email@example.com
oral / poster presentation: poster