title: The analysis of genetic aberrations in children with inherited neurometabolic and neurodevelopmental disorders.
abstract: Inherited encephalopathies include a broad spectrum of heterogeneous disorders. To provide a correct diagnosis, an integrated approach including genetic testing is warranted. We report seven patients with difficult to diagnose inborn paediatric encephalopathies. The diagnosis could not be attained only by means of clinical and laboratory investigations and MRI. Additional genetic testing was required. Cytogenetics, PCR based tests, and array-based comparative genome hybridization were performed. In 4 patients with impaired language abilities we found the presence of microduplication in the region 16q23.1 affecting two dose-sensitive genes: WWOX (OMIM 605131) and MAF (OMIM 177075) (1 case), an interstitial deletion of the 17p11.2 region (2 patients further diagnosed as Smith-Magenis syndrome), and deletion encompassing first three exons of Myocyte Enhancer Factor gene 2MEF2C (1 case). The two other cases represented progressing dystonia. Characteristic GAG deletion in DYT1 consistently with the diagnosis of torsion dystonia was confirmed in 1 case. Last enrolled patient presented with clinical picture consistent with Krabbe disease confirmed by finding of two pathogenic variants of GALC gene and the absence of mutations in PSAP. The integrated diagnostic approach including genetic testing in selected examples of complicated hereditary diseases of the brain is largely discussed in this paper.
authors.affiliation: Department of Clinical and Experimental Neuropathology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland ; Department of Child Psychiatry, Medical University of Warsaw, 00-576 Warsaw, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Szymańska
authors.affiliation: GenCentrum (Regional Center for Clinical Genetics and Modern Technologies), 25-375 Kielce, Poland.
authors.forename: Krzysztof
authors.identifier: 0000-0001-8803-646X
authors.initials: K
authors.lastname: Szczałuba
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, 02-957 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Lugowska
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Obersztyn
authors.affiliation: Department of Immunopathology of Infectious Diseases, Medical University of Warsaw, 02-091 Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Radkowski
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland.
authors.forename: Beata A
authors.initials: BA
authors.lastname: Nowakowska
authors.affiliation: Clinic of Child and Adolescent Neurology, Institute of Mother and Child, 01-211 Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kuśmierska
authors.affiliation: Department of Laboratory Diagnostics and Clinical Immunology, Medical University of Warsaw, 00-576 Warsaw, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Tryfon
authors.affiliation: Clinic of Child and Adolescent Neurology, Institute of Mother and Child, 01-211 Warsaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Demkow
mesh_terms: D000293:Adolescent; D001928:Brain Diseases, Metabolic / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods; D003581:Cytodiagnosis / Q000379:methods*; D005260:Female; D020131:Genes, Duplicate; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation; D017384:Sequence Deletion