Skip to main content
Journal cover image

Williams syndrome hemideletion and LIMK1 variation both affect dorsal stream functional connectivity.

Publication ,  Journal Article
Gregory, MD; Mervis, CB; Elliott, ML; Kippenhan, JS; Nash, T; B Czarapata, J; Prabhakaran, R; Roe, K; Eisenberg, DP; Kohn, PD; Berman, KF
Published in: Brain : a journal of neurology
December 2019

Williams syndrome is a rare genetic disorder caused by hemizygous deletion of ∼1.6 Mb affecting 26 genes on chromosome 7 (7q11.23) and is clinically typified by two cognitive/behavioural hallmarks: marked visuospatial deficits relative to verbal and non-verbal reasoning abilities and hypersocial personality. Clear knowledge of the circumscribed set of genes that are affected in Williams syndrome, along with the well-characterized neurobehavioural phenotype, offers the potential to elucidate neurogenetic principles that may apply in genetically and clinically more complex settings. The intraparietal sulcus, in the dorsal visual processing stream, has been shown to be structurally and functionally altered in Williams syndrome, providing a target for investigating resting-state functional connectivity and effects of specific genes hemideleted in Williams syndrome. Here, we tested for effects of the LIMK1 gene, deleted in Williams syndrome and important for neuronal maturation and migration, on intraparietal sulcus functional connectivity. We first defined a target brain phenotype by comparing intraparietal sulcus resting functional connectivity in individuals with Williams syndrome, in whom LIMK1 is hemideleted, with typically developing children. Then in two separate cohorts from the general population, we asked whether intraparietal sulcus functional connectivity patterns similar to those found in Williams syndrome were associated with sequence variation of the LIMK1 gene. Four independent between-group comparisons of resting-state functional MRI data (total n = 510) were performed: (i) 20 children with Williams syndrome compared to 20 age- and sex-matched typically developing children; (ii) a discovery cohort of 99 healthy adults stratified by LIMK1 haplotype; (iii) a replication cohort of 32 healthy adults also stratified by LIMK1 haplotype; and (iv) 339 healthy adolescent children stratified by LIMK1 haplotype. For between-group analyses, differences in intraparietal sulcus resting-state functional connectivity were calculated comparing children with Williams syndrome to matched typically developing children and comparing LIMK1 haplotype groups in each of the three general population cohorts separately. Consistent with the visuospatial construction impairment and hypersocial personality that typify Williams syndrome, the Williams syndrome cohort exhibited opposite patterns of intraparietal sulcus functional connectivity with visual processing regions and social processing regions: decreased circuit function in the former and increased circuit function in the latter. All three general population groups also showed LIMK1 haplotype-related differences in intraparietal sulcus functional connectivity localized to the fusiform gyrus, a visual processing region also identified in the Williams syndrome-typically developing comparison. These results suggest a neurogenetic mechanism, in part involving LIMK1, that may bias neural circuit function in both the general population and individuals with Williams syndrome.

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Brain : a journal of neurology

DOI

EISSN

1460-2156

ISSN

0006-8950

Publication Date

December 2019

Volume

142

Issue

12

Start / End Page

3963 / 3974

Related Subject Headings

  • Young Adult
  • Williams Syndrome
  • Parietal Lobe
  • Neurology & Neurosurgery
  • Nerve Net
  • Middle Aged
  • Male
  • Magnetic Resonance Imaging
  • Lim Kinases
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gregory, M. D., Mervis, C. B., Elliott, M. L., Kippenhan, J. S., Nash, T., B Czarapata, J., … Berman, K. F. (2019). Williams syndrome hemideletion and LIMK1 variation both affect dorsal stream functional connectivity. Brain : A Journal of Neurology, 142(12), 3963–3974. https://doi.org/10.1093/brain/awz323
Gregory, Michael D., Carolyn B. Mervis, Maxwell L. Elliott, J Shane Kippenhan, Tiffany Nash, Jasmin B Czarapata, Ranjani Prabhakaran, et al. “Williams syndrome hemideletion and LIMK1 variation both affect dorsal stream functional connectivity.Brain : A Journal of Neurology 142, no. 12 (December 2019): 3963–74. https://doi.org/10.1093/brain/awz323.
Gregory MD, Mervis CB, Elliott ML, Kippenhan JS, Nash T, B Czarapata J, et al. Williams syndrome hemideletion and LIMK1 variation both affect dorsal stream functional connectivity. Brain : a journal of neurology. 2019 Dec;142(12):3963–74.
Gregory, Michael D., et al. “Williams syndrome hemideletion and LIMK1 variation both affect dorsal stream functional connectivity.Brain : A Journal of Neurology, vol. 142, no. 12, Dec. 2019, pp. 3963–74. Epmc, doi:10.1093/brain/awz323.
Gregory MD, Mervis CB, Elliott ML, Kippenhan JS, Nash T, B Czarapata J, Prabhakaran R, Roe K, Eisenberg DP, Kohn PD, Berman KF. Williams syndrome hemideletion and LIMK1 variation both affect dorsal stream functional connectivity. Brain : a journal of neurology. 2019 Dec;142(12):3963–3974.
Journal cover image

Published In

Brain : a journal of neurology

DOI

EISSN

1460-2156

ISSN

0006-8950

Publication Date

December 2019

Volume

142

Issue

12

Start / End Page

3963 / 3974

Related Subject Headings

  • Young Adult
  • Williams Syndrome
  • Parietal Lobe
  • Neurology & Neurosurgery
  • Nerve Net
  • Middle Aged
  • Male
  • Magnetic Resonance Imaging
  • Lim Kinases
  • Humans