PHIP gene variants with protein modeling, interactions, and clinical phenotypes.

Variants in the pleckstrin homology domain-interacting protein (PHIP) gene are implicated in the clinical phenotype of Chung-Jansen syndrome, which includes dysmorphic features, cognitive dysfunction, aberrant behavior, and childhood onset obesity. Following a systematic literature review, 35 patients are reported to have unique PHIP variants impacting the encoded protein product. We summarize the status and frequency of these variants and relationship to clinical presentation. We also describe an additional patient with a rare, pathogenic variant due to a five base pair deletion leading to an altered codon at I307 but with a stop codon at 22 codons downstream; notably, a variant was identified at the same location as seen previously at protein position I307 in one other subject and a frameshift change at that protein position. We compare the clinical characteristics between the two patients and analyze whether certain types of gene defects impact clinical presentation in previously reported individuals. In addition, we predict structural protein models, which yielded unique differences between the wild-type and I307P-related mutant truncated proteins. Protein-protein interactions indicate involvement of POMC and related proteins with potential contribution to obesity, congenital, neuromuscular, and lipid disorders with heart, gastrointestinal, and rheumatoid diseases. With its surrounding proline-rich region, the I307P point mutation increases susceptibility to conformational rigidity and thermodynamic stability, ultimately impacting function as well as a stop codon downstream. Furthermore, the frameshift mutation seen in our patient may result in a truncated protein with a short abnormal region prior to the stop codon due to a five base pair deletion at I307 or target the protein for nonsense-mediated mRNA decay.

How do pregnant women's perceptions of obstetric forceps change according to their demographic background: a cross sectional study.

BACKGROUND: Women's attitudes towards obstetric forceps likely contribute to declining use and opportunities for residency training, but formal documentation of women's attitudes towards obstetric forceps is currently limited. A clearer understanding should help guide our attempts to preserve its use in modern obstetrics and to improve residency training. Our objective is to document women's attitudes towards obstetric forceps and the influence basic demographic variables have on those attitudes. METHODS: A cross sectional study was performed. We developed a one-time anonymous structured 5-question survey that was given to all women with low-risk pregnancies presenting to our medical center for prenatal care between October 2018-December 2018. The questionnaire asked for the woman's self-reported age, race, education level and insurance type. The five questions were as follows: (1) Do you think forceps should be used to deliver babies, (2) Is forceps safe for the baby, (3) Is forceps safe for the mother, (4) Do you think forceps can help to lower the cesarean section rate, (5) Do you think physicians in training should learn to place forceps on a real patient. We calculated means and proportions for the responses according to the overall group and various subgroups. Statistical analysis included Kruskall-Wallis or Mann-Whitney tests as appropriate. Results were also adjusted by regression using a Generalized Linear Model. Power calculation showed sample size of 384 was required. RESULTS: A total of 499 women returned the questionnaire. Response rate was 56.8% (499/878). The findings suggest that women's perceptions towards forceps are generally negative. Women with white ethnicity, college education or higher and private insurance did have more favorable views than their counterparts, but the majority still had unfavorable views. Age was not shown to have a significant effect on maternal attitude. CONCLUSION: Women's views towards forceps use in the University of Kansas Medical Center are negative and may be contributing to the decline of its use. Improving women's perceptions of forceps would require multiple different strategies rather than a single focused easily-implemented message. If forceps training continues, such training will rely on a minority of women who will accept forceps use in childbirth.

The Utility of Lower Glycemic Targets for Treating Gestational Diabetes: A Retrospective Study.

OBJECTIVE: In vivo study of glucose homeostasis in pregnancy suggests normal glucose levels are lower than current glycemic targets used in gestational diabetes. After the HAPO study results, our institution began using glycemic targets of fasting 85 mg/dL and 2-hour postprandial of 110 mg/dL. We reviewed our results. METHODS: A retrospective cohort of GDM patients that delivered at KUMC from January 2007 to May 2017 was reviewed. All patients were diagnosed with the 2-step Carpenter-Coustan thresholds. High targets were compared with low targets. The primary outcome investigated was birthweight > 90% (large for gestational age, LGA). RESULTS: 604 patients were studied, and 34% were treated with low glycemic targets. Our unadjusted results showed that the low-target group had a lower incidence of LGA infants (24.0 vs. 31.8%), higher incidence of neonatal hypoglycemia (20.7 vs. 11.6%), and inductions (39.4 vs. 20.5%). After adjustment for demographic variables, only a higher risk of inductions remained (aOR 2.54 (1.44, 4.49)). CONCLUSION: Lower glycemic targets did not produce large reductions in fetal overgrowth, but they were associated with a higher rate of inductions. As there were no observed differences in maternal or neonatal outcomes otherwise, aiming for lower glycemic targets in GDM is likely not cost-effective.