Evidence for altered neurodevelopment and neurodegeneration in Wolfram syndrome using longitudinal morphometry

Abstract Wolfram syndrome is a rare disease caused by mutations in the WFS1 gene leading to symptoms in early to mid-childhood. Brain structural abnormalities are present even in young children, but it is not known when these abnormalities arise. Such information is critical in determining optimal o...

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Autores principales:	Heather M. Lugar, Jonathan M. Koller, Jerrel Rutlin, Sarah A. Eisenstein, Olga Neyman, Anagha Narayanan, Ling Chen, Joshua S. Shimony, Tamara Hershey
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/41b133a9020c497c8b1dc5bf0c1d1452
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spelling	oai:doaj.org-article:41b133a9020c497c8b1dc5bf0c1d14522021-12-02T15:09:30ZEvidence for altered neurodevelopment and neurodegeneration in Wolfram syndrome using longitudinal morphometry10.1038/s41598-019-42447-92045-2322https://doaj.org/article/41b133a9020c497c8b1dc5bf0c1d14522019-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-42447-9https://doaj.org/toc/2045-2322Abstract Wolfram syndrome is a rare disease caused by mutations in the WFS1 gene leading to symptoms in early to mid-childhood. Brain structural abnormalities are present even in young children, but it is not known when these abnormalities arise. Such information is critical in determining optimal outcome measures for clinical trials and in understanding the aberrant neurobiological processes in Wolfram syndrome. Using voxel-wise and regional longitudinal analyses, we compared brain volumes in Wolfram patients (n = 29; ages 5–25 at baseline; mean follow-up = 3.6 years), to age and sex-equivalent controls (n = 52; ages 6–26 at baseline; mean follow-up = 2.0 years). Between groups, white and gray matter volumes were affected differentially during development. Controls had uniformly increasing volume in white matter, whereas the Wolfram group had stable (optic radiations) or decreasing (brainstem, ventral pons) white matter volumes. In gray matter, controls had stable (thalamus, cerebellar cortex) or decreasing volumes (cortex), whereas the Wolfram group had decreased volume in thalamus and cerebellar cortex. These patterns suggest that there may be early, stalled white matter development in Wolfram syndrome, with additional degenerative processes in both white and gray matter. Ideally, animal models could be used to identify the underlying mechanisms and develop specific interventions.Heather M. LugarJonathan M. KollerJerrel RutlinSarah A. EisensteinOlga NeymanAnagha NarayananLing ChenJoshua S. ShimonyTamara HersheyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Heather M. Lugar Jonathan M. Koller Jerrel Rutlin Sarah A. Eisenstein Olga Neyman Anagha Narayanan Ling Chen Joshua S. Shimony Tamara Hershey Evidence for altered neurodevelopment and neurodegeneration in Wolfram syndrome using longitudinal morphometry
description	Abstract Wolfram syndrome is a rare disease caused by mutations in the WFS1 gene leading to symptoms in early to mid-childhood. Brain structural abnormalities are present even in young children, but it is not known when these abnormalities arise. Such information is critical in determining optimal outcome measures for clinical trials and in understanding the aberrant neurobiological processes in Wolfram syndrome. Using voxel-wise and regional longitudinal analyses, we compared brain volumes in Wolfram patients (n = 29; ages 5–25 at baseline; mean follow-up = 3.6 years), to age and sex-equivalent controls (n = 52; ages 6–26 at baseline; mean follow-up = 2.0 years). Between groups, white and gray matter volumes were affected differentially during development. Controls had uniformly increasing volume in white matter, whereas the Wolfram group had stable (optic radiations) or decreasing (brainstem, ventral pons) white matter volumes. In gray matter, controls had stable (thalamus, cerebellar cortex) or decreasing volumes (cortex), whereas the Wolfram group had decreased volume in thalamus and cerebellar cortex. These patterns suggest that there may be early, stalled white matter development in Wolfram syndrome, with additional degenerative processes in both white and gray matter. Ideally, animal models could be used to identify the underlying mechanisms and develop specific interventions.
format	article
author	Heather M. Lugar Jonathan M. Koller Jerrel Rutlin Sarah A. Eisenstein Olga Neyman Anagha Narayanan Ling Chen Joshua S. Shimony Tamara Hershey
author_facet	Heather M. Lugar Jonathan M. Koller Jerrel Rutlin Sarah A. Eisenstein Olga Neyman Anagha Narayanan Ling Chen Joshua S. Shimony Tamara Hershey
author_sort	Heather M. Lugar
title	Evidence for altered neurodevelopment and neurodegeneration in Wolfram syndrome using longitudinal morphometry
title_short	Evidence for altered neurodevelopment and neurodegeneration in Wolfram syndrome using longitudinal morphometry
title_full	Evidence for altered neurodevelopment and neurodegeneration in Wolfram syndrome using longitudinal morphometry
title_fullStr	Evidence for altered neurodevelopment and neurodegeneration in Wolfram syndrome using longitudinal morphometry
title_full_unstemmed	Evidence for altered neurodevelopment and neurodegeneration in Wolfram syndrome using longitudinal morphometry
title_sort	evidence for altered neurodevelopment and neurodegeneration in wolfram syndrome using longitudinal morphometry
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/41b133a9020c497c8b1dc5bf0c1d1452
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Evidence for altered neurodevelopment and neurodegeneration in Wolfram syndrome using longitudinal morphometry

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