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Developmental dyslexia (DD) is a neurodevelopment disorder characterized by reading disabilities without apparent etiologies. Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a structural craniofacial malformation featured by isolated orofacial abnormalities. Despite substantial phenotypic differences, potential linkage between these two disorders has been suggested as prevalence of DD among NSCL/P patients was much higher than that in general populations. Previous neuroimaging studies observed impaired short-term memory in patients with DD and NSCL/P, respectively. Genetic factors have a fundamental role during neurodevelopment and craniofacial morphogenesis but there lacks of evidence to support the linkage between DD and NSCL/P at genetic level. A recent genome-wide association study in Chinese populations identified a number of genetic polymorphisms associated with NSCL/P. Herein, we selected three risk variants of NSCL/P namely rs8049367, rs4791774 and rs2235371, and performed association analysis with DD in a Chinese population consisting 631 elementary school-aged children with 288 dyslexic cases without NSCL/P and 343 healthy controls. After Bonferroni correction for multiple comparisons, the T allele of rs8049367 showed significant association with DD (OR=1.41, P=0.0085). It is an intergenic variant between CREBBP and ADCY9 located at 16p13.3. The CREBBP gene was reported to have an essential role during memory formation, although ADCY9 was involved in dental development. In future studies, understanding functional effects of rs8049367 on CERBBP and ADCY9 might contribute to explain underlying etiologies shared by DD and NSCL/P.

journal of human genetics

Genetic polymorphism of nonsyndromic cleft lip with or without cleft palate is associated with developmental dyslexia in Chinese school-aged populations