Abstract
Background. 15q duplication syndrome (Dup15q) is caused by the presence of an extra maternally derived copy of the Prader-Willi/Angelman critical region (PWACR) within chromosome 15q11.2-q13.1. The syndrome is clinically identifiable and characterized by intellectual disability, hypotonia, motor delays, autism spectrum disorder, epilepsy, and behavioral difficulties [1, 12]. The prevalence of Dup15q in the general population is unknown but may be as high as 1:5000 [10]. The syndrome most commonly occurs in one of two forms: an extra isodicentric 15 chromosome or an interstitial duplication [4]. Most reported cases concern de novo mutation.
Aim. To highlight the importance of genetic testing in patients with neurodevelopmental disorders and emphasizes the need for further research to understand the underlying genetic mechanisms of Dup15q depending on the origin of the inherited duplication.
Materials and methods. The study used next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and karyotype analysis to confirm the interstitial duplication.
Results. We present the phenotype description and diagnostic prospects of three patients from different families who inherited interstitial 15q duplication from a phenotypically healthy mother. The patients exhibited symptoms consistent with Dup15q, including intellectual disability, delayed speech, difficulty understanding spoken language, hyperactivity, epilepsy and sleep disorders.
Conclusion. The inherited interstitial duplication 15q is phenotypical presented only in case of maternal origin and vary in clinical presentation. We suggest as the first choice MLPA method as most cost and time effective in cases of Dup15q suspicion.
Publisher
Bogomolets National Medical University
Reference19 articles.
1. Al Ageeli E, Drunat S, Delanoë C, Perrin L, Baumann C, Capri Y, et al. Duplication of the 15q11-q13 region: clinical and genetic study of 30 new cases. Eur J Med Genet [Internet]. 2014. DOI: 10.1016/j.ejmg.2013.10.008
2. Conant KD, Finucane B, Cleary N, Martin A, Muss C, Delany M, et al. A survey of seizures and current treatments in 15q duplication syndrome. Epilepsia [Internet]. 2014. DOI: 10.1111/epi.12530
3. Cook EH Jr, Lindgren V, Leventhal BL, Courchesne R, Lincoln A, Shulman C, et al. Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am J Hum Genet. 1997.
4. Finucane B. M., Lusk L. , Arkilo D. 15q duplication syndrome and related disorders. University of Washington, Seattle; 2016.
5. Frohlich J, Senturk D, Saravanapandian V, Golshani P, Reiter LT, Sankar R, et al. A quantitative electrophysiological biomarker of duplication 15q11.2-q13.1 syndrome. PLoS One [Internet]. 2016. DOI: 10.1371/journal.pone.0167179