The power of the Mediator complex-Expanding the genetic architecture and phenotypic spectrum of MED12-related disorders.

MED12 is a member of the large Mediator complex that controls cell growth, development, and differentiation. Mutations in MED12 disrupt neuronal gene expression and lead to at least three distinct X-linked intellectual disability syndromes (FG, Lujan-Fryns, and Ohdo). Here, we describe six families with missense variants in MED12 (p.(Arg815Gln), p.(Val954Gly), p.(Glu1091Lys), p.(Arg1295Cys), p.(Pro1371Ser), and p.(Arg1148His), the latter being first reported in affected females) associated with a continuum of symptoms rather than distinct syndromes. The variants expanded the genetic architecture and phenotypic spectrum of MED12-related disorders. New clinical symptoms included brachycephaly, anteverted nares, bulbous nasal tip, prognathism, deep set eyes, and single palmar crease. We showed that MED12 variants, initially implicated in X-linked recessive disorders in males, may predict a potential risk for phenotypic expression in females, with no correlation of the X chromosome inactivation pattern in blood cells. Molecular modeling (Yasara Structure) performed to model the functional effects of the variants strongly supported the pathogenic character of the variants examined. We showed that molecular modeling is a useful method for in silico testing of the potential functional effects of MED12 variants and thus can be a valuable addition to the interpretation of the clinical and genetic findings.

Menstrual patterns and disorders among secondary school adolescents in Egypt. A cross-sectional survey.

BACKGROUND: To our knowledge, no large population - based studies have been performed on the topic of menstrual patterns among Egyptian adolescent in recent years. The aims of this study were to identify menstrual patterns and associated disorders as well as the sources of menstrual health knowledge among Egyptian adolescents. METHODS: A cross-sectional survey. A total of 800 questionnaires were administered to post-menarcheal Egyptian adolescents attending secondary schools in Giza, Egypt, from September 1, 2012, to December 1, 2013. Participants were asked to respond to a semi-structured questionnaire on menstrual health awareness. The questionnaire included items on girl's socio-demographic and menstrual pattern characteristics, concerning their age at menarche, menstrual cycle length and regularity, duration and amount of flow, type and severity of pain related to menstruation, need for analgesia; and symptoms suggestive of premenstrual syndrome (PMS) Main Outcome Measure: description of menstrual patterns, disorders and source of knowledge. RESULTS: Four hundred twelve (51.5 %) out of 800 adolescents completed the questionnaire. The mean age of the girls was 14.67 ± 1.7 years. Mean age at menarche was 12.49 ± 1.20 years. 382 respondents reported various menstrual disorders, giving a prevalence rate of 95 %. Dysmenorrhea was the most prevalent (93 %) menstrual disorder in our sample, followed by PMS (65 %), and abnormal cycle lengths (43 %). Menstrual disorders interfered with social and academic life of 33 and 7.7 % of respondents respectively. Most participants lacked menstrual health knowledge and only 8.9 % of girls reported consulting a physician. CONCLUSION: To the best of our knowledge, this is one of the largest studies on menstrual pattern and disorders among Egyptian adolescent girls. Our Findings of the present study are consistent with other studies and reported higher than expected prevalence of menstrual disorders.

Significance of assay of nucleated RBCs in umbilical cord blood in neonates with meconium-stained amniotic fluid.

BACKGROUND: Approximately 8-15% of all infants are born with evidence of meconium-stained amniotic fluid (MSAF). MSAF is a potentially serious sign of fetal compromise and may indicate fetal hypoxia Objectives and aim of the work: The present study was designed to evaluate the relationship between meconium stained amniotic fluid and fetal nucleated red blood cell counts. As well, we aim to evaluate the relationship between the presence of meconium in amniotic fluid and Apgar scores in neonates. SUBJECTS AND METHODS: A prospectively case-controlled study was performed on 40 women with clear amniotic fluid as control and 40 women with meconium-stained amniotic fluid as the study group. At delivery, 2 ml of umbilical cord blood was collected and analyzed for nucleated red blood cell (NRBC). RESULTS: The mean NRBC counts in meconium-stained amniotic fluid was significantly higher than the control group (18.35 ± 7.7 and 9.6 ± 4.96), respectively (p < .001). There were statistically significant differences concerning 1- and 5-min Apgar scores with lower values in the MSAF group (p < .001 and .001, respectively). CONCLUSION: Our results support previous studies which indicate the presence of meconium can be associated with chronic fetal hypoxia as demonstrated by elevated fetal NRBC levels.

Nuchal cord: impact of umbilical artery Doppler indices on intrapartum and neonatal outcomes: a prospective cohort study.

Background/objective: The purpose of this study is to investigate the use of a more biologic parameter for evaluation of the effect of nuchal cord tightness; the study of blood flow in the umbilical arteries of nuchal cord using Doppler ultrasonography. Methods: This prospective cohort study was conducted at Ain Shams University Maternity Hospital, Cairo, Egypt in the period between August 2015 and August 2017. Hundred primigravidas were recruited with nuchal cord diagnosed by Doppler ultrasonography; whereas the rest of the study population was included in the "Control group". Doppler velocimetry study was then performed on a free-floating loop of the umbilical cord and Doppler indices were calculated. Both groups were followed up during labor: intrapartum events, mode of delivery, and neonatal outcome were recorded. Results: Intrapartum fetal heart rate abnormalities were significantly more common in the nuchal cord group compared to the control group. The overall cardiotocography category was significantly more commonly reflecting abnormal fetal heart rate patterns in the nuchal cord group compared to the control group with 46.74% of the nuchal group patients falling within the "suspicious - pathological - need urgent intervention" categories. Intervention rate was significantly higher in the nuchal cord group than the control group (33.69 versus 21.84%). Moreover, incidence of intrapartum fetal heart rate abnormalities and intervention rate were significantly higher in the nuchal cord with abnormal Doppler subgroup compared to both nuchal cord with normal Doppler subgroup and the control group; with a calculated number needed to harm of 2.11. Conclusions: In view of these results, it might be concluded that umbilical cord tightness affecting fetal hemodynamics (expressed by changes in umbilical artery Doppler) might be a determinate factor affecting the intrapartum course.

Different-sized duplications of Xq28, including MECP2, in three males with mental retardation, absent or delayed speech, and recurrent infections.

In XY males, duplication of any part of the X chromosome except the pseudoautosomal region leads to functional disomy of the corresponding genes. We describe three unrelated male patients with mental retardation (MR), absent or delayed speech, and recurrent infections. Using high-resolution comparative genomic hybridization (HR-CGH), whole genome array comparative genomic hybridization (array CGH), fluorescent in situ hybridization (FISH), and multiplex ligation probe amplification (MLPA), we have identified and characterized two different unbalanced Xq27.3-qter translocations on the Y chromosome (approx. 9 and 12 Mb in size) and one submicroscopic interstitial duplication (approx. 0.3-1.3 Mb) involving the MECP2 gene. Despite the differences in size of the duplicated segments, the patients share a clinical phenotype that overlaps with the features described in patients with MECP2 duplication. Our data confirm previous observations that MECP2 is the most important dosage-sensitive gene responsible for neurologic development in patients with duplications on the distal part of chromosome Xq.

Addition of growth hormone to the microflare stimulation protocol among women with poor ovarian response.

OBJECTIVE: To assess the efficacy of adding growth hormone (GH) to the microflare stimulation protocol among women with poor ovarian response. METHODS: A parallel, open-label, randomized controlled trial was conducted among patients with poor ovarian response who attended a center in Cairo, Egypt, between July 10 and December 31, 2014. Participants were randomly assigned using a computer program (random block size of 4-8) to undergo the microflare protocol with or without GH. Primary outcomes were the mean numbers of mature oocytes retrieved and fertilized. Analyses were done per protocol: women with cycle cancellations were excluded. RESULTS: The analysis included 72 women in the GH group and 73 in the microflare only group. The mean number of oocytes collected was 7.2±1.5 in the GH group versus 4.7±1.2 in the microflare only group (P<0.001). The mean number of metaphase II oocytes was 5.2±1.2 in the GH group and 2.8±1.0 in the microflare only group (P<0.001). The mean number of fertilized oocytes was higher in the GH group (4.2±1.1) than in the microflare only group (2.5±0.7; P<0.001). CONCLUSION: Addition of GH to the microflare stimulation protocol provided some potential benefits to women with poor ovarian response. However, further studies are required before it could be recommended for routine clinical use. ClinicalTrials.gov:NCT02185326.

Limited experience in early management of genitourinary tract fistulas.

INTRODUCTION: Genitourinary tract fistulas commonly occur as a complication of gynecologic operations. Vesicovaginal, ureterovaginal, and uterovesical fistulas are the most common fistulas occurring after these operations. In this study, we report the results of early repair of genitourinary fistulas using a retropubic, extraperitoneal, transvesical approach. TECHNICAL CONSIDERATIONS: In our study, 20 women with a genitourinary tract fistula (12 with vesicovaginal, 6 with ureterovaginal, and 2 with uterovesical fistulas) were diagnosed and treated within 2 weeks after a gynecologic operation. RESULTS: All patients reported a high quality of life postoperatively. None of the patients had urinary leakage after their fistula repair. Urinary urgency occurred after surgery in 7 patients. No urinary tract infections were reported. Follow-up of the patients showed no incidence of ureteral stricture and preservation of upper urinary tract function. CONCLUSIONS: The results of our study have shown that early repair of genitourinary tract fistulas results in a high quality of life, few postoperative complications, and a high success rate and preservation of renal function.

Genotype-phenotype associations for ARX gene duplication in X-linked mental retardation.

We screened 165 mentally retarded patients for ARX gene 428-451 base pair (bp) duplication. Eighteen individuals from five families were found to carry the duplication, and all had intellectual impairment. Twelve presented with focal hand dystonia, while six patients had EEG abnormalities including seizures. Other symptoms included speech difficulties (4/18), testis enlargement (4/18), lower limb spasticity or foot dystonia (4/18), and facial telangiectasia (3/18). These features confirm the pleiotropic effect of the duplication.

Pregnancy wastage.

PIP: This study of early and late pregnancy wastage performed at 3 Egyptian teaching hospitals to assess the magnitude of the problem, detect its causes and recommend measures that will eliminate such causes and reduce pregnancy wastage. As defined here, pregnancy wastage includes abortion and perinatal mortality. In Egypt early pregnancy wastage varies between 23.8%-36.57%, and late pregnancy wastage between 15.3%-88%. The results of these studies show that spontaneous abortion is high among low socio-economic class and high parity groups. The incidence of spontaneous abortion is found to vary with wife's education, husband's education, wife's age, age at marriage, parity and order of living children. The perinatal mortality rate (PNMR) showed variation with socioeconomic factors, biomedical factors, primary antenatal condition of expectant mothers and manpower training. Results indicate a high PNMR among mothers who were not booked at a hospital and only came to the hospital for the 1st time in labour, among those patients in labour who were referred to the hospital by traidtional birth attendants, as opposed to a general practitioner, and among non-paying patients. Moreover, the PNMR was high for non-educated mothers and for those who had never received any antenatal care. The highest PNMR was among those women who had received 8 or more antenatal visits as they represent the high risk patients. With respect to biomedical factors, the PNMR was found to vary with the maternal age groups, parity, outcome of the last pregnancy and gestational age. Additional contributing factors were pre-existing maternal diseases like anemia, toxemia of pregnancy, diabetes mellitus and antepartum hemorrhage. Finally, analysis of PNMR in this study shows that PNMR varies with the degree of skill of the birth attendant and his/her awareness of the problem of PNMR and the hospital's recording system. The analysis of perinatal mortality cases revealed that most of the underlying causes are preventable. The analysis also showed that 45% of the cases occured in the antepartum period, 30% in the intrapartum period and 25% in the postpartum period. The significant loss in the postpartum period is a strong reason for the obstetrician to work in close contact with the neonatologist to reduce the PNMR. The pregnancy wastage rate in Egypt and other developing countries can be markedly reduced by bettering socioeconomic standards, promoting the use of effective contraception, improving health services, health education obstetric practice, and manpower training, and by establishing neonatal units and a proper recording system.^ieng