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PMID: 12954984 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A candidate gene for developmental dyslexia encodes a nuclear tetratricopeptide repeat domain protein dynamically regulated in brain.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 20 ·2003-09-30 ·Pages 11553-8

Taipale M, Kaminen N, Nopola-Hemmi J, Haltia T, Myllyluoma B, Lyytinen H, Muller K, Kaaranen M, Lindsberg PJ, Hannula-Jouppi K, Kere J

Abstract

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.

MeSH Terms
Base Sequence Blotting, Southern Brain/metabolism Chromosomes, Human, Pair 15 Cytoskeletal Proteins DNA, Complementary Dyslexia/genetics Female Gene Expression Regulation Genetic Predisposition to Disease Humans Immunohistochemistry In Situ Hybridization, Fluorescence Male Molecular Sequence Data Nerve Tissue Proteins/chemistry,genetics Nuclear Proteins/chemistry,genetics Pedigree Polymorphism, Genetic Repetitive Sequences, Amino Acid Sequence Homology, Amino Acid
Chemicals
Cytoskeletal Proteins DNA, Complementary DNAAF4 protein, human Nerve Tissue Proteins Nuclear Proteins
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Taipale Mikko
Department of Medical Genetics, University of Helsinki, 00014 Helsinki, Finland.
Kaminen Nina
Nopola-Hemmi Jaana
Haltia Tuomas
Myllyluoma Birgitta
Lyytinen Heikki
Muller Kurt
Kaaranen Minna
Lindsberg Perttu J
Hannula-Jouppi Katariina
Kere Juha
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.1833911100
Published
2003-09-30
Epub
2003-00-03
Pages
11553-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC208796
Subset
IM
Databases
GENBANK
AC013355, AF337549, AH012450, AH012451, AH012452, AH012453, AK005832, AY178583, AY178584, AY178585, AY178586, AY178587, AY178588, AY178589, AY178590, AY178591, AY178592, AY178593, AY178594, AY178595, AY178596, AY178597, AY178598, AY178599, AY178600, AY178601, AY178602, AY178603, AY178604, AY178605, AY178606, AY178607, AY178608, AY178609, AY178610, AY178611, AY178612, AY178613, AY178614, AY178615, AY178616, AY178617, AY178618, BG242087
Corrections
CommentIn
PMID: 14506298
External Links
PubMed source DOI: 10.1073/pnas.1833911100 PMC Full Text View journal details
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