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DOI: 10.1055/s-0040-1722686
Specific Cognitive Changes due to Hippocalcin Alterations? A Novel Familial Homozygous Hippocalcin Variant Associated with Inherited Dystonia and Altered Cognition
Funding M.F. reports personal fees from Novartis outside the submitted work. T.P. reports grants from Austrian Childhood Cancer Organization, Austrian Childhood Cancer Organization-Parents' Initiative, Gemeinsame Gesundheitsziele aus dem Rahmen-Pharmavertrag, NF-Kinder, Occursus, and 42virtual outside the submitted work. W.M.S. reports personal fees from AveXis Inc. and PTC Therapeutics Inc. outside the submitted work.
Abstract
Background Recent research suggested an hippocalcin (HPCA)-related form of DYT2-like autosomal recessive dystonia. Two reports highlight a broad spectrum of the clinical phenotype. Here, we describe a novel HPCA gene variant in a pediatric patient and two affected relatives.
Methods Whole exome sequencing was applied after a thorough clinical and neurological examination of the index patient and her family members. Results of neuropsychological testing were analyzed.
Results Whole exome sequencing revealed a novel homozygous missense variant in the HPCA gene [c.182C>T p.(Ala61Val)] in our pediatric patient and the two affected family members. Clinically, the cases presented with dystonia, dysarthria, and jerky movements. We observed a particular cognitive profile with executive dysfunctions in our patient, which corresponds to the cognitive deficits that have been observed in the patients previously described.
Conclusion We present a novel genetic variant of the HPCA gene associated with autosomal recessive dystonia in a child with childhood-onset dystonia supporting its clinical features. Furthermore, we propose specific HPCA-related cognitive changes in homozygous carriers, underlining the importance of undertaking a systematic assessment of cognition in HPCA-related dystonia.
Publikationsverlauf
Eingereicht: 08. Juli 2020
Angenommen: 23. Oktober 2020
Artikel online veröffentlicht:
28. Januar 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
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