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Children exposed to maternal sickle cell disease (SCD) have many theoretical risks for developmental disorders, but little is known about long-term outcomes for these children. We used the Boston Birth Cohort to compare developmental outcomes between children exposed to maternal SCD and matched, unexposed controls. Children with exposure to maternal SCD had increased risk of attention deficit hyperactivity disorder (OR 5.12, 95% CI 1.36-19.19, p  = 0.02) and obesity (OR 2.74, 95% CI 1.10-6.87, p  = 0.03). In utero and/or environmental exposures may help explain these findings. Further studies of outcomes of children born to women with SCD are needed., Competing Interests: Martha Brucato, Eboni Lance, and Xiaobin Wang have no conflicts of interest to declare. Lydia H. Pecker reports a consultancy for Forma Therapeutics outside the submitted work. Sophie Lanzkron received research funds to her institution from Pfizer, Ironwood, and Global Blood Therapeutics outside the submitted work., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Kabuki syndrome is a monogenic disorder caused by loss of function variants in either of two genes encoding histone-modifying enzymes. We performed targeted sequencing in a cohort of 27 probands with a clinical diagnosis of Kabuki syndrome. Of these, 12 had causative variants in the two known Kabuki syndrome genes. In 2, we identified presumptive loss of function de novo variants in KMT2A (missense and splice site variants), a gene that encodes another histone modifying enzyme previously exclusively associated with Wiedermann-Steiner syndrome. Although Kabuki syndrome is a disorder of histone modification, we also find alterations in DNA methylation among individuals with a Kabuki syndrome diagnosis relative to matched normal controls, regardless of whether they carry a variant in KMT2A or KMT2D or not. Furthermore, we observed characteristic global abnormalities of DNA methylation that distinguished patients with a loss of function variant in KMT2D or missense or splice site variants in either KMT2D or KMT2A from normal controls. Our results provide new insights into the relationship of genotype to epigenotype and phenotype and indicate cross-talk between histone and DNA methylation machineries exposed by inborn errors of the epigenetic apparatus.

The separation of the optic neuroepithelium into future retina and retinal pigment epithelium (RPE) is a critical event in early eye development in vertebrates. Here we show in mice that the transcription factor PAX6, well-known for its retina-promoting activity, also plays a crucial role in early pigment epithelium development. This role is seen, however, only in a background genetically sensitized by mutations in the pigment cell transcription factor MITF. In fact, a reduction in Pax6 gene dose exacerbates the RPE-to-retina transdifferentiation seen in embryos homozygous for an Mitf null allele, and it induces such a transdifferentiation in embryos that are either heterozygous for the Mitf null allele or homozygous for an RPE-specific hypomorphic Mitf allele generated by targeted mutation. Conversely, an increase in Pax6 gene dose interferes with transdifferentiation even in homozygous Mitf null embryos. Gene expression analyses show that, together with MITF or its paralog TFEC, PAX6 suppresses the expression of Fgf15 and Dkk3. Explant culture experiments indicate that a combination of FGF and DKK3 promote retina formation by inhibiting canonical WNT signaling and stimulating the expression of retinogenic genes, including Six6 and Vsx2. Our results demonstrate that in conjunction with Mitf/Tfec Pax6 acts as an anti-retinogenic factor, whereas in conjunction with retinogenic genes it acts as a pro-retinogenic factor. The results suggest that careful manipulation of the Pax6 regulatory circuit may facilitate the generation of retinal and pigment epithelium cells from embryonic or induced pluripotent stem cells., Competing Interests: The authors have declared that no competing interests exist.

The establishment of Globodera rostochiensis Rol populations was examined under greenhouse conditions. The probability of G. rostochiensis population establishment was calculated from the number of plants that produced new cysts with viable eggs following inoculation with various numbers of eggs of different ages. Probability of population establishment was positively correlated with inoculum density but was not affected by the age of eggs used in these experiments. The probability of G. rostochiensis establishment ranged from 5% at densities of 2 eggs/pot to 100% at densities of 25 eggs/pot or greater. At densities of 3 eggs/pot and beyond, there was no correlation between inoculum density and the number of viable eggs/new cyst. Also, the number of plants that produced new cysts was a function of inoculum density and not age of eggs. Juveniles from eggs 1 year old or older were equally as infective as were those from eggs in newly developed cysts (4 months old).

The effects of aldicarb, oxamyl, 1,3-D, and plastic mulch (solarization) on soil population densities of the golden nematode (GN) Globodera rostochiensis was assessed in field and microplot experiments with different soil types. Oxamyl was evaluated in both soil and foliar treatments, whereas aldicarb, 1,3-D, and solarization were applied only to soil. Soil applications of aldicarb and oxamyl resulted in reduced nematode populations after GN-susceptible potatoes in plots with initial population densities (Pi) of > 20 and 7.5 eggs/cm(3) soil, respectively, but nematode populations increased in treated soil when Pi were less than 20 and 7.5 eggs/cm(3)soil. In clay loam field plots with Pi of 19-76 eggs/cm(3) soil, nematode densities increased even with repeated foliar applications of oxamyl, whereas nematode populations at Pi greater than 76 eggs/cm(3) soil were reduced by foliar oxamyl. Treatment with 1,3-D or solarization, singly or in combination, reduced GN soil population densities regardless of soil type or Pi. Temperatures lethal to GN were achieved 5 cm deep under clear plastic but not 10 or 15 cm deep.