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DCDC2 genetic variants and susceptibility to developmental dyslexia

Marino, Ceciliaa,d; Meng, Haiyinge; Mascheretti, Sarac; Rusconi, Mariannab; Cope, Nataliee; Giorda, Robertob; Molteni, Massimoa; Gruen, Jeffrey R.e

Psychiatric Genetics:
doi: 10.1097/YPG.0b013e32834acdb2
Original Articles
Abstract

Objective(s): Developmental dyslexia is a heritable condition, with genetic factors accounting for 44–75% of the variance in performance tests of reading component subphenotypes. Compelling genetic linkage and association evidence supports a quantitative trait locus in the 6p21.3 region that encodes a gene called DCDC2. In this study, we explored the contribution of two DCDC2 markers to dyslexia, related reading and memory phenotypes in nuclear families of Italian origin.

Methods: The 303 nuclear families recruited on the basis of having a proband with developmental dyslexia have been studied with 6p21.3 markers, BV677278 and rs793862. Marker-trait association was investigated by the quantitative transmission disequilibrium test (version 2.5.1) that allows for the analyses of quantitative traits. Seven phenotypes were used in association analyses, that is, word and nonword reading, word and nonword spelling, orthographic choice, memory, and the affected status based on inclusion criteria.

Results: Quantitative transmission disequilibrium test analyses yielded evidence for association between reading skills and the BV677278 deletion (empirical P-values=0.025–0.029) and between memory and BV677278 allele 10 (empirical P-value=0.0001).

Conclusion: Our result adds further evidence in support of DCDC2 contributing to the deficits in developmental dyslexia. More specifically, our data support the view that DCDC2 influences both reading and memory impairments thus shedding further light into the etiologic basis and the phenotypic complexity of developmental dyslexia.

Author Information

aDepartment of Child Psychiatry

bMolecular Biology Laboratory, Scientific Institute Eugenio Medea, Bosisio Parini

cVita Salute San Raffaele University, The Academic Centre for the Study of Behavioural Plasticity, Milan, Italy

dCentre de Recherche Université Laval Robert-Giffard, Québec, Canada

eYale Child Health Research Center, Yale University School of Medicine, New Haven, CT, USA

Correspondence to Dr Cecilia Marino, MD, PhD, Istituto Scientifico Eugenio Medea, Via don Luigi Monza, 20, 23842 Bosisio Parini (LC), Italy Tel: +39 031 877813; fax: +39 031 877499; e-mail: cecilia.marino@bp.lnf.it

Received September 3, 2010

Accepted June 22, 2011

© 2012 Lippincott Williams & Wilkins, Inc.