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From the Cover
GENETICS
A candidate gene for developmental dyslexia encodes a nuclear tetratricopeptide repeat domain protein dynamically regulated in brain

Mikko Taipale ^* , Nina Kaminen ^* , Jaana Nopola-Hemmi ^*   ¶, Tuomas Haltia ^||, Birgitta Myllyluoma , Heikki Lyytinen ^**, Kurt Muller ^**, Minna Kaaranen ^**, Perttu J. Lindsberg , Katariina Hannula-Jouppi ^*, and Juha Kere ^*  

^*Department of Medical Genetics, University of Helsinki, 00014 Helsinki, Finland; Department of Pediatric Neurology, Hospital for Children and Adolescents, University of Helsinki, 00014 Helsinki, Finland; ^¶Department of Pediatrics, Jorvi Hospital, 02740 Espoo, Finland; ^||Institute of Biomedicine/Biochemistry, Biomedicum Helsinki, University of Helsinki, 00014 Helsinki, Finland; ^**Department of Psychology and Child Research Centre, University of Jyväskylä, 40014 Jyväskylä, Finland; Department of Neurology, Neuroscience Program, Biomedicum Helsinki, Helsinki University Central Hospital, 00014 Helsinki, Finland; and Department of Biosciences at Novum and Clinical Research Centre, Karolinska Institutet, 14157 Huddinge, Sweden

Communicated by Albert de la Chapelle, Ohio State University, Columbus, OH, June 24, 2003 (received for review December 23, 2002)

Approximately 3–10% of people have specific difficulties in reading, despite adequate intelligence, education, and social environment. We report here the characterization of a gene, DYX1C1 near the DYX1 locus in chromosome 15q21, that is disrupted by a translocation t(2;15)(q11;q21) segregating coincidentally with dyslexia. Two sequence changes in DYX1C1, one involving the translation initiation sequence and an Elk-1 transcription factor binding site (–3G A) and a codon (1249G T), introducing a premature stop codon and truncating the predicted protein by 4 aa, associate alone and in combination with dyslexia. DYX1C1 encodes a 420-aa protein with three tetratricopeptide repeat (TPR) domains, thought to be protein interaction modules, but otherwise with no homology to known proteins. The mouse Dyx1c1 protein is 78% identical to the human protein, and the nonhuman primates differ at 0.5–1.4% of residues. DYX1C1 is expressed in several tissues, including the brain, and the protein resides in the nucleus. In human brain, DYX1C1 protein localizes to a fraction of cortical neurons and white matter glial cells. We conclude that DYX1C1 should be regarded as a candidate gene for developmental dyslexia. Detailed study of its function may open a path to understanding a complex process of development and maturation of the human brain.

Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF337549 for the DYX1C1 cDNA sequence, AC013355 and AC013355 for the genomic sequence of the BAC clones 178D12 and RP-11-178D12, BG242087 and AK005832 for the mouse Dyx1c1 cDNA sequence, and AY178583–AY178618 and AH012450–AH012453 for the primate DYX1C1 sequences).

See commentary on page 11190.

Present address: European Molecular Biology Laboratory, Gene Expression Programme, 69117 Heidelberg, Germany.

N.K. and J.N.-H. contributed equally to this work.

To whom correspondence should be sent at the address. E-mail: juha.kere{at}biosci.ki.se.

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Related Commentary in PNAS:

The first candidate gene for dyslexia: Turning the page of a new chapter of research

Elena L. Grigorenko
PNAS 2003 100: 11190-11192. [Extract] [Full Text]  

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