Developmental dyslexia is a language learning disorder that affects approximately 4–10% of the population. A number of candidate dyslexia susceptibility genes have been identified, including DCDC2 and KIAA0319 on Chromosome (Chr) 6p22.2 and DYX1C1 on Chr 15q21. Embryonic knockdown of the function of homologs of these genes in rat neocortical projection cell progenitors by in utero electroporation of plasmids encoding small hairpin RNA (shRNA) revealed that all three genes disrupted neuronal migration to the neocortex. Specifically, this disruption would result in heterotopia formation (Dyx1c1 and Kiaa0319) and/or overmigration past their expected laminar location (Dyx1c1 and Dcdc2). In these experiments, neurons normally destined for the upper neocortical laminæ were transfected on embryonic day (E) 15.5, and we designed experiments to test whether these migration phenotypes were the result of targeting a specific type of projection neuron. We transfected litters with Dcdc2 shRNA, Dyx1c1 shRNA, Kiaa0319 shRNA, or fluorescent protein (as a control) at each of three gestational ages (E14.5, E15.5, or E16.5). Pups were allowed to come to term, and their brains were examined at 3 weeks of age for the position of transfected cells. We found that age of transfection did not affect the percentage of unmigrated neurons—transfection with Kiaa0319 shRNA resulted in heterotopia formation at all three ages. Overmigration of neurons transfected with Dcdc2 shRNA, while present following transfections at the later ages, did not occur following E14.5 transfections. These results are considered in light of the known functions of each of these candidate dyslexia susceptibility genes.

Developmental dyslexia, the most common childhood learning disorder, is highly heritable, and recent studies have identified KIAA0319-Like (KIAA0319L) as a candidate dyslexia susceptibility gene at the 1p36-34 (DYX8) locus. In this experiment, we investigated the anatomical effects of knocking down this gene during rat corticogenesis. Cortical progenitor cells were transfected using in utero electroporation on embryonic day (E) 15.5 with plasmids encoding either: (1) Kiaa0319l shRNA, (2) an expression construct for human KIAA0319L, (3) Kiaa0319l shRNA + KIAA0319L expression construct (rescue), or (4) controls (scrambled Kiaa0319l shRNA or empty expression vector). Mothers were injected with BrdU at either E13.5, E15.5, or E17.5. Disruption of Kiaa0319l function (by knockdown, overexpression, or rescue) resulted in the formation of large nodular periventricular heterotopia in approximately 25% of the rats, and these heterotopia can be seen as early as postnatal day 1. Only a small subset of heterotopic neurons had been transfected, indicating non-cell autonomous effects of the transfection. Most heterotopic neurons were generated in mid- to late-gestation, and laminar markers suggest that they were destined for upper cortical laminæ. Finally, we found that transfected neurons in the cerebral cortex were located in their expected laminæ. These results indicate that KIAA0319L is the fourth of four candidate dyslexia susceptibility genes that is involved in neuronal migration, which supports the association of abnormal neuronal migration with developmental dyslexia.

Ancillary testing is useful in isolated mild ventriculomegaly. Follow-up MRI and chromosome abnormality testing specifically provided clinically useful information. Although there were no cases of maternal infection, screening may be an important component in management. © 2017 John Wiley & Sons, Ltd.

stratified into the following four periods for analysis: 24-33 weeks, 34-36 weeks, 37-40 weeks and 40-42 weeks. The risks of stillbirth associated with each BMI class was compared to normal weight pregnancies for each gestational period using proportional hazard regression models. The indirect effect of obesity on stillbirth mediated through GDM and GHTN were then estimated. The ratio of the indirect effect to direct effect provided an estimate of the role these factors played in the causal pathway between obesity and stillbirth. RESULTS: After all exclusions 3,279,846 births remained for analysis, including 11,023 stillbirths. The effect of GDM in the causal pathway to stillbirth was similar for all BMI classes and peaked between 37-39 weeks. Between 37-39 weeks, the effect of BMI on stillbirth mediated through GDM ranged from 56% in obesity class II to 64% in the extreme obesity group. Whereas between 40-42 weeks, the mediated effects through GDM ranged from 33% in the extreme obesity group to 49% in obesity class II. In contrast, the stillbirth risk mediated through GHTN increased with BMI class and peaked between 40-42 weeks. Between 37-39 weeks, the risk of stillbirth mediated through GHTN was 22% in the overweight group, and increased with BMI to 49% in the extreme obesity group. Whereas between 40-42 weeks, the mediated effects through GHTN increased from 30% in the overweight group to 81% in the extreme obesity group. CONCLUSION: GDM and GHTN are both significant mediators in the causal pathway between BMI and stillbirth, although at different gestational periods. GDM had the strongest effect in the early term period; whereas GHTN had the greatest effect in the late term period.