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Your search keyword '"Kangas, S. M. (Salla M.)"' showing total 2 results
Start Over Author "Kangas, S. M. (Salla M.)" Publisher john wiley & sons
2 results on '"Kangas, S. M. (Salla M.)"'

1. Epidemiological, clinical, and genetic characteristics of paediatric genetic white matter disorders in Northern Finland

Author

Knuutinen, O. A. (Oula A.), Oikarainen, J. H. (Jaakko H.), Suo-Palosaari, M. H. (Maria H.), Kangas, S. M. (Salla M.), Rahikkala, E. J. (Elisa J.), Pokka, T. M. (Tytti M-L.), Moilanen, J. S. (Jukka S.), Hinttala, R. M. (Reetta M. L.), Vieira, P. M. (Päivi M.), Uusimaa, J. M. (Johanna M.), Knuutinen, O. A. (Oula A.), Oikarainen, J. H. (Jaakko H.), Suo-Palosaari, M. H. (Maria H.), Kangas, S. M. (Salla M.), Rahikkala, E. J. (Elisa J.), Pokka, T. M. (Tytti M-L.), Moilanen, J. S. (Jukka S.), Hinttala, R. M. (Reetta M. L.), Vieira, P. M. (Päivi M.), and Uusimaa, J. M. (Johanna M.)

Abstract

Aim: To examine the epidemiological, clinical, and genetic characteristics of paediatric patients with genetic white matter disorders (GWMDs) in Northern Finland. Method: A longitudinal population-based cohort study was conducted in the tertiary catchment area of Oulu University Hospital from 1990 to 2019. Patients were identified retrospectively by International Statistical Classification of Diseases and Related Health Problems codes in hospital records and prospectively by attending physicians. Inclusion criteria were children younger than 18 years with defined GWMDs or genetic disorders associated with white matter abnormalities (WMAs) on brain magnetic resonance imaging. Results: Eighty patients (mean age [SD] at the end of the study 11y [8y 6mo], range 0–35y; 45 males, 35 females) were diagnosed with a defined GWMD. The cumulative childhood incidence was 30 per 100 000 live births. Regarding those patients with 49 distinct GWMDs, 20% had classic leukodystrophies and 80% had genetic leukoencephalopathies. The most common leukodystrophies were cerebral adrenoleukodystrophy, Krabbe disease, and Salla disease. Additionally, 29 patients (36%) had genetic aetiologies not previously associated with brain WMAs or they had recently characterised GWMDs, including SAMD9L- and NHLRC2-related neurological disorders. Aetiology was mitochondrial in 21% of patients. The most common clinical findings were motor developmental delay, intellectual disability, hypotonia, and spasticity. Interpretation: The cumulative childhood incidence of childhood-onset GWMDs was higher than previously described. Comprehensive epidemiological and natural history data are needed before future clinical trials are undertaken.

Published
2021

2. Homozygous TAF1C variants are associated with a novel childhood‐onset neurological phenotype

Author

Knuutinen, O. (Oula), Pyle, A. (Angela), Suo-Palosaari, M. (Maria), Duff, J. (Jennifer), Froukh, T. (Tawfiq), Lehesjoki, A.-E. (Anna-Elina), Kangas, S. M. (Salla M.), Cassidy, J. (James), Maraqa, L. (Latifa), Keski-Filppula, R. (Riikka), Kokkonen, H. (Hannaleena), Uusimaa, J. (Johanna), Horvath, R. (Rita), and Vieira, P. (Päivi)

Subjects
TATAbinding protein associated factors, Pol1 transcription initiation complex proteins, brain atrophy, infantile spasms
Abstract

TATA‐box binding protein associated factor, RNA polymerase I subunit C (TAF1C) is a component of selectivity factor 1 belonging to RNA polymerase I (Pol I) transcription machinery. We report two unrelated patients with homozygous TAF1C missense variants and an early onset neurological phenotype with severe global developmental delay. Clinical features included lack of speech and ambulation and epilepsy. MRI of the brain demonstrated widespread cerebral atrophy and frontal periventricular white matter hyperintensity. The phenotype resembled that of a previously described variant of UBTF, which encodes another transcription factor of Pol I. TAF1C variants were located in two conserved amino acid positions and were predicted to be deleterious. In patient‐derived fibroblasts, TAF1C mRNA and protein expression levels were substantially reduced compared with healthy controls. We propose that the variants impairing TAF1C expression are likely pathogenic and relate to a novel neurological disease. This study expands the disease spectrum related to Pol I transcription machinery, associating the TAF1C missense variants with a severe neurological phenotype for the first time.

Published
2020

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