A study published in the Oct. 20 issue of the New England Journal of Medicine outlines the discovery of a genetic abnormality in a nine-year-old boy with learning difficulties and speech problems from northern Alberta. By using some of the latest genetic screening methods designed to look for differences in the amount of DNA in particular chromosomes, the researchers discovered that the boy carries additional copies (termed duplication) of around 27 genes on chromosome 7. This is only the second instance of the identification of a single chromosome region linked to specific language impairment.
The boy can understand what is said to him at the level of a seven-year-old but his expressive language and speech are at the level of a two-and-a-half-year-old. "Our results show that changes in the copy number of specific genes can dramatically influence human language abilities," says senior author Lucy Osborne, a U of T professor of medicine. "Based on our findings, we are expanding the study to assess the frequency of this DNA duplication in children with expressive language delay."
The chromosome 7 region that is duplicated in this boy is exactly the same as that which is deleted in Williams-Beuren syndrome (WBS), a neurodevelopmental disorder. While patients with WBS exhibit mild mental retardation, they also have strength in expressive language, alongside very poor performance in tasks involving spatial construction, such as drawing. In striking contrast, this patient could form virtually no complete words but showed normal spatial ability. "For example, if asked to tell us what animal has long ears and eats carrots, he could only pronounce the r, of the word rabbit but was able to draw the letter on the blackboard and add features such as whiskers," Osborne says.
This mutation - an addition of 1.5 million DNA base pairs - was predicted several years ago to exist by Osborne and her collaborator Stephen Scherer of The Hospital for Sick Children and U of T. "While estimated to be present in more than a half million people worldwide, the duplication has evaded detection since the disease was unknown until now, but also because finding this type of mutation is technically challenging," explains Martin Somerville, director of the Molecular Diagnostic Laboratory at the Stollery Children's Hospital. Uncovering the duplication sheds light on which genes are necessary for normal expressive language. "Language impairment was thought to be caused by the interaction of multiple genes on different chromosomes, but in this case our discovery implicates a specific location on chromosome 7," Somerville says. "In order to know how to treat a disease you have to know its cause, so this is a significant step in the right direction."
Other authors on the study are Edwin Young and Wayne Loo, Institute of Medical Science and Department of Molecular & Medical Genetics, University of Toronto; Stephen Bamforth and Margaret Lilley, Department of Medical Genetics, University of Alberta; Carolyn Mervis and Ella Peregrine, Department of Psychological and Brain Sciences, University of Louisville; Miguel del Campo and Luis Pérez-Jurado, Unitat de Genética, Departament Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona; and Colleen Morris, Department of Pediatrics, University of Nevada School of Medicine; and Eul-Ju Seo and Stephen Scherer, Program in Genetics & Genomic Biology, The Hospital for Sick Children, Toronto and U of T.
This study was supported by grants from the Canadian Institutes of Health Research (CIHR) and the Sick Kids Foundation, the Spanish ministries of health and science and technology, Genome Canada/Ontario Genomics Institute, the National Institute of Neurological Disorders and Stroke and the National Institute of Child Health and Human Development. Scherer is a CIHR investigator and an international scholar of the Howard Hughes Medical Institute. Osborne is a CIHR research scholar.
University of Toronto
Professor Lucy Osborne
Faculty of Medicine
University of Toronto
Public Affairs, University of Alberta