title: Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients.
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.
authors: Institute of Education, University of London, London, UK.
authors: Hannah
authors: H
authors: Broadbent
authors: Institute of Education, University of London, London, UK.
authors: Emily K
authors: EK
authors: Farran
authors: Birkbeck Centre for Brain and Cognitive Development, University of London, London, UK.
authors: Esther
authors: E
authors: Chin
authors: Genetic Medicine, St. Mary's Hospital, Manchester, UK.
authors: Kay
authors: K
authors: Metcalfe
authors: Genetic Medicine, St. Mary's Hospital, Manchester, UK.
authors: May
authors: M
authors: Tassabehji
authors: Royal Devon and Exeter Foundation Trust, Exeter, UK ; Penninsula College of Medicine and Dentistry, Universities of Exeter and Plymouth, Exeter, UK.
authors: Peter
authors: P
authors: Turnpenny
authors: Royal Devon and Exeter Foundation Trust, Exeter, UK ; Penninsula College of Medicine and Dentistry, Universities of Exeter and Plymouth, Exeter, UK.
authors: Francis
authors: F
authors: Sansbury
authors: Birkbeck Centre for Brain and Cognitive Development, University of London, London, UK.
authors: Emma
authors: E
authors: Meaburn
authors: Birkbeck Centre for Brain and Cognitive Development, University of London, London, UK.
authors: Annette
authors: A
authors: Karmiloff-Smith
keywords: GTF2I; GTF2IRD1; LIMK1; Navigation; Visuospatial cognition; Williams syndrome