DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children

Developmental dyslexia is a complex reading and writing disorder with strong genetic components. In previous genetic studies about dyslexia, a number of candidate genes have been identified. These include DCDC2, which has repeatedly been associated with developmental dyslexia in various European and American populations. However, data regarding this relationship are varied according to population. The Uyghur people of China represent a Eurasian population with an interesting genetic profile. Thus, this group may provide useful information about the association between DCDC2 gene polymorphisms and dyslexia. In the current study, we examined genetic data from 392 Uyghur children aged 8–12 years old from the Xinjiang Uyghur Autonomous Region of China. Participants included 196 children with dyslexia and 196 grade-, age-, and gender-matched controls. DNA was isolated from oral mucosal cell samples and fourteen single nucleotide polymorphisms（rs6456593, rs1419228, rs34647318, rs9467075, rs793862, rs9295619, rs807701, rs807724, rs2274305, rs7765678, rs4599626, rs6922023, rs3765502, and rs1087266） in DCDC2 were screened via the SNPscan method. We compared SNP frequencies in five models（Codominant, Dominant, Recessive, Heterozygote advantage, and Allele） between the two groups by means of the chi-squared test. A single-locus analysis indicated that, with regard to the allele frequency of these polymorphisms, three SNPs（rs807724, rs2274305, and rs4599626） were associated with dyslexia. rs9467075 and rs2274305 displayed significant associations with developmental dyslexia under the dominant model. rs6456593 and rs6922023 were significantly associated with developmental dyslexia under the dominant model and in the heterozygous genotype. Additionally, we discovered that the T-G-C-T of the four-marker haplotype（rs9295619-rs807701-rs807724-rs2274305） and the T-A of the two-marker haplotype（rs3765502-1087266） were significantly different between cases and controls. Thus, we conclude that DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children.

Understanding recurrent pregnancy loss:recent advances on its etiology,clinical diagnosis,and management

Recurrent pregnancy loss(RPL)has become an important reproductive health issue worldwide.RPL affects about 2%–3%of reproductive-aged women,and makes serious threats to women’s physical and mental health.However,the etiology of approximately 50%of RPL cases remains unknown(unexplained RPL),which poses a big challenge for clinical management of these patients.RPL has been widely regarded as a complex disease where its etiology has been attributed to numerous factors.Heretofore,various risk factors for RPL have been identified,such as maternal ages,genetic factors,anatomical structural abnormalities,endocrine dysfunction,prethrombotic state,immunological factors,and infection.More importantly,development and applications of next generation sequencing technology have significantly expanded opportunities to discover chromosomal aberrations and single gene variants responsible for RPL,which provides new insight into its pathogenic mechanisms.Furthermore,based upon patients’diagnostic evaluation and etiologic diagnosis,specific therapeutic recommendations have been established.This review will highlight current understanding and recent advances on RPL,with a special focus on the immunological and genetic etiologies,clinical diagnosis and therapeutic management.

PRKG1 mutation identified by whole-exome sequencing:a potential genetic etiology for He-Zhao deficiency

Objective:He-Zhao deficiency was originally described as a severe type of nonsyndromic hypodontia,and the causative gene locus was mapped to chromosome 10q11.2.The aim of this study was to identify potential genetic mutations that could cause He-Zhao deficiency.Methods:Patients with He-Zhao deficiency and their unaffected relatives of the large pedigree were investigated.The whole-exome sequencing using next-generation sequencing was employed to identify genetic variants.The data generated from the whole-exome sequencing using the Illumina Novaseq 6000 system were further analyzed by Burrows-Wheeler Aligner software,Sequence Alignment/Map tools and ANNOVAR tool.In vitro luciferase assay was used to investigate the effect of the detected mutation on gene expression.R environment was used to conduct t-tests.The study protocol was approved by the Research Ethics Committee of Bio-X Institutes,Shanghai Jiao Tong University(M2011004).Results:The exomes of five patients with He-Zhao deficiency and two of their unaffected relatives identified a mutation in PRKG1αas the molecular etiology of the disease.The variant c.-144 C>A of PRKG1 isoform 1 cosegregated with permanent tooth agenesis in 93 family members who were older than 12,at which time the primary teeth should have been replaced with permanent teeth.Functional studies suggested that the mutant allele promotes gene transcription by increasing its promoter activity.Conclusion:c.-144 C>A variant of PRKG1αinvolving odontoclast-associated root resorption is responsible for He-Zhao deficiency,unlike other forms of hypodontia,which typically involve odontoblast dysfunction.