Towards a Better Molecular Diagnosis of FMR1-Related Disorders—A Multiyear Experience from a Reference Lab

The article summarizes over 20 years of experience of a reference lab in fragile X mental retardation 1 gene (FMR1) molecular analysis in the molecular diagnosis of fragile X spectrum disorders. This includes fragile X syndrome (FXS), fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS), which are three different clinical conditions with the same molecular background. They are all associated with an expansion of CGG repeats in the 5′UTR of FMR1 gene. Until 2016, the FMR1 gene was tested in 9185 individuals with the pre-screening PCR, supplemented with Southern blot analysis and/or Triplet Repeat Primed PCR based method. This approach allowed us to confirm the diagnosis of FXS, FXPOI FXTAS in 636/9131 (6.96%), 4/43 (9.3%) and 3/11 (27.3%) of the studied cases, respectively. Moreover, the FXS carrier status was established in 389 individuals. The technical aspect of the molecular analysis is very important in diagnosis of FXS-related disorders. The new methods were subsequently implemented in our laboratory. This allowed the significance of the Southern blot technique to be decreased until its complete withdrawal. Our experience points out the necessity of implementation of the GeneScan based methods to simplify the testing procedure as well as to obtain more information for the patient, especially if TP-PCR based methods are used

Association between Parity and Preterm Birth—Retrospective Analysis from a Single Center in Poland

Preterm births and parity are two medical areas that seem to be entirely different from each other. The aim of this study was to analyze the relationships between parity and maternal and neonatal outcomes associated with preterm birth. This study involved a retrospective analysis of electronic medical records from St. Sophia Hospital in Warsaw (Poland). This study was conducted among women who gave birth to preterm infants between 1 January 2017 and 31 December 2021. A total of 2043 cases of preterm births were included in the final analysis. A higher odds ratio of preterm birth in primiparas was found in women living in a city/town (OR = 1.56) and having secondary (OR = 1.46) and higher education (OR = 1.82). Multiparas who gave birth to preterm infants were more frequently diagnosed with gestational diabetes (19.69%) than primiparas. Multiparas were more likely to give birth to preterm infants who received an Apgar score of ≤7 both at 1 and 5 min after birth (25.80% and 15.34%). The results of our study emphasize the differences between primiparas and multiparas who give birth to preterm infants. Knowledge of these differences is essential to improve the perinatal care provided to mothers and their infants

Retrospective Analysis of the Factors Affecting the Induction of Childbirth in 4350 Women from a Single Center in Warsaw, Poland

Labor induction is one of the most common procedures performed during childbirth, on average in 20–30% of all pregnant women. The aim of this paper was to perform a retrospective analysis of the factors influencing the induction of childbirth. The data provide population-based evidence for Poland (Masovian Voivodeship). The electronic patient records of a hospital in Warsaw were used to create an anonymous retrospective database of all deliveries from 2015 to 2020. The study included an analysis of two groups of patients. The study group consisted of patients with labor induction—4350 cases, and the control group of patients with spontaneous contractions—20,345. The factors influencing the lower frequency of labor induction in the study group were previous cesarean section (OR = 0.73, 95% CI: 0.64–0.84, p < 0.05) and a higher number of deliveries (OR = 0.74, 95% CI: 0.68–0.80, p < 0.05). It is necessary to conduct further research about obstetric procedures used during childbirth, such as induction of childbirth, to reduce the risk of complications and improve the perinatal care of the mother and the neonate

Episiotomy for Medical Indications during Vaginal Birth—Retrospective Analysis of Risk Factors Determining the Performance of This Procedure

The WHO (World Health Organization) recommends that the percentage of perineal incisions should not exceed 10%, indicating that this is a good goal to achieve, despite the fact that it is still a frequently used medical intervention in Poland. The risk factors for perineal incision that have been analyzed so far in the literature allow, among others, to limit the frequency of performing this procedure. Are they still valid? Have there been new risk factors that we should take into account? We have conducted this study to find the risk factors for performing perineal incision that would reduce the frequency of this procedure. The aim of the study was to check whether the risk factors that were analyzed in the literature are still valid, to find new risk factors for perineal incisions and to compare them among Polish women. This was a single-center retrospective case-control study. The electronic patient records of Saint Sophia’s Hospital in Warsaw, Poland, a tertiary hospital was used to create an anonymous retrospective database of all deliveries from 2015 to 2020. The study included the analysis of two groups, the study group of patients who had had an episiotomy, and the control group-patients without an episiotomy in cases where an episiotomy was indicated. A logistic regression model was developed to assess the risk factors for perineal laceration. Independent risk factors for episiotomy in labor include oxytocin use in the second stage of labor (OR (Odds Ratio) = 6.00; 95% CI (Confidence Interval): 4.76–7.58), the supply of oxytocin in the first and the second stage of labor (OR = 3.18; 95% CI: 2.90–3.49), oxytocin use in the first stage of labor (OR = 2.72; 95% CI: 2.52–3.51), state after cesarean section (OR = 2.97; 95% CI: 2.52–3.51), epidural anesthesia use (OR = 1.77; 95% CI: 1.62–1.93), male gender (OR = 1.10; 95% CI: 1.02–1.19), and prolonged second stage of labor (OR = 1.01; 95% CI: 1.01–1.01). A protective factor against the use of an episiotomy was delivery in the Birth Centre (OR = 0.43; 95% CI: 0.37–0.51) and mulitpara (OR = 0.31; 95% CI: 0.27–0.35). To reduce the frequency of an episiotomy, it is necessary consider the risk factors of performing this procedure in everyday practice, e.g., limiting the use of oxytocin or promoting alternative places of delivery

WDR13: A Novel Gene Implicated in Non-Syndromic Intellectual Disability

Investigating novel genetic variants involved in intellectual disability (ID) development is essential. X-linked intellectual disability (XLID) accounts for over 10% of all cases of ID in males. XLID genes are involved in many cellular pathways and processes. Some of them are not specific to the development and functioning of the neural system. The implementation of exome sequencing simplifies the search for novel variants, especially those less expected. Here, we describe a nonsense variant of the XLID gene, WDR13. The mutation c.757C>T (p.Arg253Ter) was uncovered by X-chromosome exome sequencing in males with a familial form of intellectual disability. Quantitative PCR (qPCR) analysis showed that variant c.757C>T caused a significant decrease in WDR13 expression in the patient\u27s fibroblast. Moreover, it dysregulated other genes linked to intellectual disability, such as FMR1, SYN1, CAMK2A, and THOC2. The obtained results indicate the pathogenic nature of the detected variant and suggest that the WDR13 gene interacts with other genes essential for the functioning of the nervous system, especially the synaptic plasticity process

Towards a Better Molecular Diagnosis of FMR1-Related Disorders—A Multiyear Experience from a Reference Lab

The article summarizes over 20 years of experience of a reference lab in fragile X mental retardation 1 gene (FMR1) molecular analysis in the molecular diagnosis of fragile X spectrum disorders. This includes fragile X syndrome (FXS), fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS), which are three different clinical conditions with the same molecular background. They are all associated with an expansion of CGG repeats in the 5′UTR of FMR1 gene. Until 2016, the FMR1 gene was tested in 9185 individuals with the pre-screening PCR, supplemented with Southern blot analysis and/or Triplet Repeat Primed PCR based method. This approach allowed us to confirm the diagnosis of FXS, FXPOI FXTAS in 636/9131 (6.96%), 4/43 (9.3%) and 3/11 (27.3%) of the studied cases, respectively. Moreover, the FXS carrier status was established in 389 individuals. The technical aspect of the molecular analysis is very important in diagnosis of FXS-related disorders. The new methods were subsequently implemented in our laboratory. This allowed the significance of the Southern blot technique to be decreased until its complete withdrawal. Our experience points out the necessity of implementation of the GeneScan based methods to simplify the testing procedure as well as to obtain more information for the patient, especially if TP-PCR based methods are used

Expanding the genetics and phenotypic spectrum of Lysine-specific demethylase 5C (KDM5C): a report of 13 novel mutations

Lysine-specific demethylase 5C (KDM5C) has been identified as an important chromatin remodeling gene, contributing to X-linked neurodevelopmental disorders (NDDs). The KDM5C gene, located in the Xp22 chromosomal region, encodes the H3K4me3-me2 eraser involved in neuronal plasticity and dendritic growth. Here we report 30 individuals carrying 13 novel and one previously identified KDM5C variants. Our cohort includes the first reported case of somatic mosaicism in a male carrying a KDM5C nucleotide substitution, and a dual molecular finding in a female carrying a homozygous truncating FUCA1 alteration together with a de novo KDM5C variant. With the use of next generation sequencing strategies, we detected 1 frameshift, 1 stop codon, 2 splice-site and 10 missense variants, which pathogenic role was carefully investigated by a thorough bioinformatic analysis. The pattern of X-chromosome inactivation was found to have an impact on KDM5C phenotypic expression in females of our cohort. The affected individuals of our case series manifested a neurodevelopmental condition characterized by psychomotor delay, intellectual disability with speech disorders, and behavioral features with particular disturbed sleep pattern; other observed clinical manifestations were short stature, obesity and hypertrichosis. Collectively, these findings expand the current knowledge about the pathogenic mechanisms leading to dysfunction of this important chromatin remodeling gene and contribute to a refinement of the KDM5C phenotypic spectrum