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Purpose Mediator is a multiprotein complex that allows the transfer of genetic information from DNA binding proteins to the RNA polymerase II during transcription initiation. MED12L is a subunit of the kinase module, which is one of the four sub-complexes of the mediator complex. Other subunits of the kinase module have been already implicated in intellectual disability, namely MED12, MED13L, MED13 and CDK19. Methods We describe an international cohort of seven affected individuals harboring variants involving MED12L identified by array CGH, exome or genome sequencing. Results All affected individuals presented with intellectual disability and/or developmental delay, including speech impairment. Other features included autism spectrum disorder, aggressive behavior, corpus callosum abnormality and mild facial morphological features. Three individuals had a MED12L deletion or duplication. The other four individuals harbored single nucleotide variants (one nonsense, one frameshift and two splicing variants). Functional analysis confirmed a moderate and significant alteration of RNA synthesis in two individuals. Conclusion Overall data suggest that MED12L haploinsufficiency is responsible for intellectual disability and transcriptional defect. Our findings confirm that the integrity of this kinase module is a critical factor for neurological development.

OBJECTIVES: This study examined differences between nurses and paraprofessionals in implementation of a home visiting program for low-income, first-time parents during pregnancy and the first 2 years of the child's life. METHODS: Mothers were randomly assigned to either a nurse-visited (n = 236) or a paraprofessional-visited (n = 244) condition. Nurse- and paraprofessional-visited families were compared on number and length of visits, topics covered, number of program dropouts, and relationship with home visitor. RESULTS: On average, nurses completed more visits than paraprofessionals (28 vs 23; P < .001) and spent a greater proportion of time on physical health issues during pregnancy (38% vs 27%; P < .001) and on parenting issues during infancy (46% vs 32%; P < .001). Paraprofessionals conducted visits that lasted longer and spent a greater proportion of time on environmental health and safety issues (15% vs 7% pregnancy; 15% vs 8% infancy; P < .001). While home visitors were viewed equally positively by mothers, nurses had fewer dropouts than did paraprofessionals (38% vs 48%; P = .04). More paraprofessional-visited families than nurse-visited families experienced staff turnover. CONCLUSIONS: Nurses and paraprofessionals, even when using the same model, provide home visiting services in different ways.

The adaptation for paraprofessional visitors of a home visitation model originally developed for nurses is described. There are several hypothesized benefits of using paraprofessional home visitors, including power as role models and increased empathy with clients. Challenges inherent in employing paraprofessionals include limited formal education and resulting lack of credibility among professional care providers, difficulties in acculturation to the workplace, and learning how to effectively focus their commitment to and identification with the community. These challenges result in the need for unique training and sensitive and consistent supervision. Implementation data from the randomized trial of home visitation in Denver indicate that paraprofessional visitors conducted the program according to the prescribed visitation schedule and covered the material appropriately. Differences that emerged between nurse and paraprofessional visitors regarding content covered are discussed and suggestions are made for future programmatic considerations. © 1997 John Wiley & Sons, Inc.

Objective. To examine the effectiveness of home visiting by paraprofessionals and by nurses as separate means of improving maternal and child health when both types of visitors are trained in a program model that has demonstrated effectiveness when delivered by nurses.Methods. A randomized, controlled trial was conducted in public- and private-care settings in Denver, Colorado. One thousand one hundred seventy-eight consecutive pregnant women with no previous live births who were eligible for Medicaid or who had no private health insurance were invited to participate. Seven hundred thirty-five women were randomized to control, paraprofessional, or nurse conditions.Nurses completed an average of 6.5 home visits during pregnancy and 21 visits from birth to the children’s second birthdays. Paraprofessionals completed an average of 6.3 home visits during pregnancy and 16 visits from birth to the children’s second birthdays.The main outcomes consisted of changes in women’s urine cotinine over the course of pregnancy; women’s use of ancillary services during pregnancy; subsequent pregnancies and births, educational achievement, workforce participation, and use of welfare; mother-infant responsive interaction; families’ home environments; infants’ emotional vulnerability in response to fear stimuli and low emotional vitality in response to joy and anger stimuli; and children’s language and mental development, temperament, and behavioral problems.Results. Paraprofessional-visited mother-child pairs in which the mother had low psychological resources interacted with one another more responsively than their control-group counterparts (99.45 vs 97.54 standard score points). There were no other statistically significant paraprofessional effects.In contrast to their control-group counterparts, nurse-visited smokers had greater reductions in cotinine levels from intake to the end of pregnancy (259.0 vs 12.32 ng/mL); by the study child’s second birthday, women visited by nurses had fewer subsequent pregnancies (29% vs 41%) and births (12% vs 19%); they delayed subsequent pregnancies for longer intervals; and during the second year after the birth of their first child, they worked more than women in the control group (6.83 vs 5.65 months).Nurse-visited mother-child pairs interacted with one another more responsively than those in the control group (100.31 vs 98.99 standard score points). At 6 months of age, nurse-visited infants, in contrast to their control-group counterparts, were less likely to exhibit emotional vulnerability in response to fear stimuli (16% vs 25%) and nurse-visited infants born to women with low psychological resources were less likely to exhibit low emotional vitality in response to joy and anger stimuli (24% vs 40% and 13% vs 33%). At 21 months, nurse-visited children born to women with low psychological resources were less likely to exhibit language delays (7% vs 18%); and at 24 months, they exhibited superior mental development (90.18 vs 86.20 Mental Development Index scores) than their control-group counterparts. There were no statistically significant program effects for the nurses on women’s use of ancillary prenatal services, educational achievement, use of welfare, or their children’s temperament or behavior problems.For most outcomes on which either visitor produced significant effects, the paraprofessionals typically had effects that were about half the size of those produced by nurses.Conclusions. When trained in a model program of prenatal and infancy home visiting, paraprofessionals produced small effects that rarely achieved statistical or clinical significance; the absence of statistical significance for some outcomes is probably attributable to limited statistical power to detect small effects. Nurses produced significant effects on a wide range of maternal and child outcomes.