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Mahler, E.A.* ; Johannsen, J.* ; Tsiakas, K.* ; Kloth, K.* ; Lüttgen, S.* ; Mühlhausen, C.* ; Alhaddad, B.* ; Haack, T.B.* ; Strom, T.M. ; Kortüm, F.* ; Meitinger, T. ; Muntau, A.C.* ; Santer, R.* ; Kubisch, C.* ; Lessel, D.* ; Denecke, J.* ; Hempel, M.*

Exome sequencing in children undiagnosed developmental delay and neurological illness.

Dtsch. Arztebl. Int. 116, 197-204 (2019)
Verlagsversion DOI
Free journal
Background: In developed countries, global developmental disorders are encountered in approximately 1% of all children. The causes are manifold, and no exogenous cause can be identified in about half of the affected children. The parallel investigation of the coding sequences of all genes of the affected individual (whole exome sequencing, WES) has developed into a successful diagnostic method for identifying the cause of the problem. It is not yet clear, however, when WES should best be used in routine clinical practice in order to exploit the potential of this method to the fullest.Methods: In an interdisciplinary study, we carried out standardized clinical phenotyping and a systematic genetic analysis (WES of the index patient and his or her parents, so-called trio WES) in 50 children with developmental disturbances of unclear etiology and with nonspecific neurological manifestations.Results: In 21 children (42% of the collective), we were able to identify the cause of the disorder by demonstrating a mutation in a gene known to be associated with disease. Three of these children subsequently underwent specific treatment. In 22 other children (44%), we detected possibly etiological changes in candidate genes not currently known to be associated with human disease.Conclusion: Our detection rate of at least 42% is high in comparison with the results obtained in other studies from Germany and other countries to date and implies that WES can be used to good effect as a differential diagnostic tool in pediatric neurology. WES should be carried out in both the index patient and his or her parents (trio-WES) and accompanied by close interdisciplinary collaboration of human geneticists and pediatricians, by comprehensive and targeted phenotyping (also after the diagnosis is established), and by the meticulous evaluation of all gene variants.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter De-novo Mutations; Human Phenotype Ontology; Clinical Exome; Intellectual-disability; Recommendations; Identification; Percentiles; Prevalence; Disorders; Disease
ISSN (print) / ISBN 1866-0452
e-ISSN 1866-0452
Quellenangaben Band: 116, Heft: 12, Seiten: 197-204 Artikelnummer: , Supplement: ,
Verlag Dt. Ärzte-Verl.
Verlagsort Dieselstrabe 2, Postfach 400265, D-50859 Cologne, Germany
Begutachtungsstatus Peer reviewed