Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients

2.50
Hdl Handle:
http://hdl.handle.net/11287/593825
Title:
Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients
Authors:
Broadbent, H.; Farran, E. K.; Chin, E.; Metcalfe, K.; Tassabehji, M.; Turnpenny, Peter D.; Sansbury, Francis H.; Meaburn, E.; Karmiloff-Smith, A.
Abstract:
BACKGROUND: Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive. METHODS: WE REPORT ON VISUOSPATIAL COGNITION IN TWO INDIVIDUALS WITH CONTRASTING PARTIAL DELETIONS IN THE WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted. RESULTS: Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB's atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion. CONCLUSIONS: Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed.
Citation:
J Neurodev Disord. 2014;6(1):18.
Publisher:
BioMed Central
Journal:
Journal of neurodevelopmental disorders
Issue Date:
1-Jul-2014
URI:
http://hdl.handle.net/11287/593825
DOI:
10.1186/1866-1955-6-18
PubMed ID:
25057328
Additional Links:
http://jneurodevdisorders.biomedcentral.com/articles/10.1186/1866-1955-6-18
Note:
This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.
Type:
Journal Article
Language:
eng
ISSN:
1866-1947
Appears in Collections:
2014 RD&E publications; Clinical Genetics (Peninsula Genetics)

Full metadata record

DC FieldValue Language
dc.contributor.authorBroadbent, H.en
dc.contributor.authorFarran, E. K.en
dc.contributor.authorChin, E.en
dc.contributor.authorMetcalfe, K.en
dc.contributor.authorTassabehji, M.en
dc.contributor.authorTurnpenny, Peter D.en
dc.contributor.authorSansbury, Francis H.en
dc.contributor.authorMeaburn, E.en
dc.contributor.authorKarmiloff-Smith, A.en
dc.date.accessioned2016-01-19T12:35:25Zen
dc.date.available2016-01-19T12:35:25Zen
dc.date.issued2014-07-01en
dc.identifier.citationJ Neurodev Disord. 2014;6(1):18.en
dc.identifier.issn1866-1947en
dc.identifier.pmid25057328en
dc.identifier.doi10.1186/1866-1955-6-18en
dc.identifier.urihttp://hdl.handle.net/11287/593825en
dc.description.abstractBACKGROUND: Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive. METHODS: WE REPORT ON VISUOSPATIAL COGNITION IN TWO INDIVIDUALS WITH CONTRASTING PARTIAL DELETIONS IN THE WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted. RESULTS: Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB's atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion. CONCLUSIONS: Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed.en
dc.language.isoengen
dc.publisherBioMed Centralen
dc.relation.urlhttp://jneurodevdisorders.biomedcentral.com/articles/10.1186/1866-1955-6-18en
dc.titleGenetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patientsen
dc.typeJournal Articleen
dc.identifier.journalJournal of neurodevelopmental disordersen
dc.description.noteThis article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.en

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