Expert Reviews in Molecular Medicine

 

Research Article

Rearrangements of the Williams–Beuren syndrome locus: molecular basis and implications for speech and language development

Lucy R. Osbornea1 c1 and Carolyn B. Mervisa2

a1 Department of Medicine, University of Toronto, Ontario, Canada.

a2 Department of Psychological and Brain Sciences, University of Louisville, KY 40292, USA.

Abstract

The Williams–Beuren syndrome (WBS) locus on human chromosome 7q11.23 is flanked by complex chromosome-specific low-copy repeats that mediate recurrent genomic rearrangements of the region. Common genomic rearrangements arise through unequal meiotic recombination and result in complex but distinct behavioural and cognitive phenotypes. Deletion of 7q11.23 results in WBS, which is characterised by mild to moderate intellectual disability or learning difficulties, with relative cognitive strengths in verbal short-term memory and in language and extreme weakness in visuospatial construction, as well as anxiety, attention-deficit hyperactivity disorder and overfriendliness. By contrast, duplication results in severely delayed speech and expressive language, with relative strength in visuospatial construction. Although deletion and duplication of the WBS region have very different effects, both cause forms of language impairment and suggest that dosage-sensitive genes within the region are important for the proper development of human speech and language. The spectrum and frequency of genomic rearrangements at 7q11.23 presents an exceptional opportunity to identify gene(s) directly involved in human speech and language development.

Correspondence

c1 *Corresponding author: Lucy R. Osborne, Department of Medicine, University of Toronto, 7360 Medical Sciences Bldg, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada. Tel: +1 416 946 5804; Fax: +1 416 978 8765; E-mail: lucy.osborne@utoronto.ca