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Johannesen, K.* ; Mitter, D.* ; Janowski, R. ; Roth, C.* ; Toulouse, J.* ; Poulat, A.* ; Ville, D.M.* ; Chatron, N.* ; Brilstra, E.* ; Geleijns, K.* ; Born, A.P.* ; McLean, S.* ; Nugent, K.* ; Baynam, G.* ; Poulton, C.* ; Dreyer, L.* ; Gration, D.* ; Schulz, S.* ; Dieckmann, A.* ; Helbig, K.L.* ; Merkenschlager, A.* ; Jamra, R.* ; Finck, A.* ; Gardella, E.* ; Hjalgrim, H.* ; Mirzaa, G.* ; Brancati, F.* ; Bierhals, T.* ; Denecke, J.* ; Hempel, M.* ; Lemke, J.R.* ; Rubboli, G.* ; Muschke, P.* ; Guerrini, R.* ; Vetro, A.* ; Niessing, D. ; Lesca, G.* ; Moller, R.S.*

Defining and expanding the phenotype of QARS-associated developmental epileptic encephalopathy.

Neurol. Genet. 5:e373 (2019)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
Objective The study is aimed at widening the clinical and genetic spectrum and at assessing genotype-phenotype associations in QARS encephalopathy. Methods Through diagnostic gene panel screening in an epilepsy cohort, and recruiting through GeneMatcher and our international network, we collected 10 patients with biallelic QARS variants. In addition, we collected data on 12 patients described in the literature to further delineate the associated phenotype in a total cohort of 22 patients. Computer modeling was used to assess changes on protein folding. Results Biallelic pathogenic variants in QARS cause a triad of progressive microcephaly, moderate to severe developmental delay, and early-onset epilepsy. Microcephaly was present at birth in 65%, and in all patients at follow-up. Moderate (14%) or severe (73%) developmental delay was characteristic, with no achievement of sitting (85%), walking (86%), or talking (90%). Additional features included irritability (91%), hypertonia/spasticity (75%), hypotonia (83%), stereotypic movements (75%), and short stature (56%). Seventy-nine percent had pharmacoresistant epilepsy with mainly neonatal onset. Characteristic cranial MRI findings include early-onset progressive atrophy of cerebral cortex (89%) and cerebellum (61%), enlargement of ventricles (95%), and age-dependent delayed myelination (88%). A small subset of patients displayed a less severe phenotype. Conclusions These data revealed first genotype-phenotype associations and may serve for improved interpretation of new QARS variants and well-founded genetic counseling.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Transfer-rna-synthetase; Ilae Commission; Position Paper; Mutations; Classification; Deficiency; Features
ISSN (print) / ISBN 2376-7839
e-ISSN 2376-7839
Zeitschrift Neurology Genetics
Quellenangaben Band: 5, Heft: 6, Seiten: , Artikelnummer: e373 Supplement: ,
Verlag American Academy of Neurology
Verlagsort Minneapolis, Minn.
Begutachtungsstatus Peer reviewed