Timed rolling and rising tests in Duchenne muscular dystrophy ambulant boys: a feasibility study.

BACKGROUND: Functional activities are extensively used in motor assessments of patients with Duchenne muscular dystrophy. The role of timed items has been reported as an early prognostic factor for disease progression. However, there are two functional activities that are not widely assessed in clinical practice among Duchenne muscular dystrophy patients: rolling and bed rising. This study aimed to investigate whether the 360-degree roll (roll) and supine to sit-to-edge (bed rise) measurements are feasible tools reflecting the functional status of ambulatory DMD children by establishing possible correlations between validated measures: the Vignos Scale (VS), timed rise from floor and the 6-Minute Walk Test (6MWT). METHODS: A total of 32 ambulant boys with DMD were assessed using timed items, the 6MWT and VS. RESULTS: The roll and bed rise are correlated with each other. The 6MWT, the floor rise and VS are correlated with the roll and with the bed rise. CONCLUSIONS: Findings offer preliminary empirical evidence addressing feasibility and safety of roll and bed rise measurements. There is a potential clinical utility of these tests in assessing functional status of DMD ambulant patients.

Generation of human induced pluripotent stem cell line derived from Becker muscular dystrophy patient with CRISPR/Cas9-mediated correction of DMD gene mutation.

Becker muscular dystrophy (BMD) is an X-linked recessive disorder caused by in-frame deletions in the dystrophin gene (DMD), leading to progressive muscle degeneration and weakness. We generated a human induced pluripotent stem cell (hiPSC) line from a BMD patient. BMD hiPSCs were then engineered by CRISPR/Cas9-mediated knock-in of missing exons 3-9 of DMD gene. Obtained hiPSC line may be a valuable tool for investigating the mechanisms underlying BMD pathogenesis.

Variants in the WDR44 WD40-repeat domain cause a spectrum of ciliopathy by impairing ciliogenesis initiation.

WDR44 prevents ciliogenesis initiation by regulating RAB11-dependent vesicle trafficking. Here, we describe male patients with missense and nonsense variants within the WD40 repeats (WDR) of WDR44, an X-linked gene product, who display ciliopathy-related developmental phenotypes that we can model in zebrafish. The patient phenotypic spectrum includes developmental delay/intellectual disability, hypotonia, distinct craniofacial features and variable presence of brain, renal, cardiac and musculoskeletal abnormalities. We demonstrate that WDR44 variants associated with more severe disease impair ciliogenesis initiation and ciliary signaling. Because WDR44 negatively regulates ciliogenesis, it was surprising that pathogenic missense variants showed reduced abundance, which we link to misfolding of WDR autonomous repeats and degradation by the proteasome. We discover that disease severity correlates with increased RAB11 binding, which we propose drives ciliogenesis initiation dysregulation. Finally, we discover interdomain interactions between the WDR and NH2-terminal region that contains the RAB11 binding domain (RBD) and show patient variants disrupt this association. This study provides new insights into WDR44 WDR structure and characterizes a new syndrome that could result from impaired ciliogenesis.

Can Pre-Pregnancy Body Mass Index and Maternal Exercise Affect Birth and Neonatal Outcomes-A Cross Sectional Study.

There has been a dramatic worldwide increase in the prevalence of obesity or overweight and physical inactivity in women of reproductive age. Growing evidence suggests that pre-pregnancy maternal abnormal body mass index (BMI) and lower physical activity level are associated with poor maternal health and perinatal outcomes. The aim of this study was to assess how self-perceived exercise and pre-pregnancy BMI are associated with preterm birth, low birth weight, and type of birth. We conducted a retrospective cross-sectional study of 394 Polish women in the postpartum period. We used a questionnaire with the structure of the medical interview. To analyze factors related to birth outcomes, we used the Pearson's Chi-squared test of independence and odds ratio (OR), with a corresponding 95% confidence interval (CI), followed by a multiple logistic regression. Women who reported being physically active before pregnancy (p = 0.00) and during pregnancy (p = 0.03) were more likely to give birth on time and had a lower incidence of very-premature and extremely premature births compared to inactive women. Importantly, they were more likely to have vaginal birth (p = 0.03). Pre-pregnancy BMI influenced the week of delivery, i.e., inadequate, too-high BMI contributed to an increase in the percentage of premature births [OR (95% CI) = 1.19 (1.06; 1.34)]. The findings indicate that promoting physical activity and weight management remains a priority in public health policy, and women of childbearing age should be encouraged to adopt or maintain an active and healthy lifestyle during pregnancy in order to avoid sedentary- and obesity-associated risks affecting birth and newborns' health.

Prematurity and Low Birth Weight and Their Impact on Childhood Growth Patterns and the Risk of Long-Term Cardiovascular Sequelae.

Preterm birth (before 37 completed weeks of gestation) is a global health problem, remaining the main reason for neonatal mortality and morbidity. Improvements in perinatal and neonatal care in recent decades have been associated with a higher survival rate of extremely preterm infants, leading to a higher risk of long-term sequelae in this population throughout life. Numerous surveillance programs for formerly premature infants continue to focus on neurodevelopmental disorders, while long-term assessment of the impact of preterm birth and low birth weight on child growth and the associated risk of cardiovascular disease in young adults is equally necessary. This review will discuss the influence of prematurity and low birth weight on childhood growth and cardiovascular risk in children, adolescents and young adults. The risk of cardiovascular and metabolic disorders is increased in adult preterm survivors. In early childhood, preterm infants may show elevated blood pressure, weakened vascular growth, augmented peripheral vascular resistance and cardiomyocyte remodeling. Increased weight gain during the early postnatal period may influence later body composition, promote obesity and impair cardiovascular results. These adverse metabolic alterations contribute to an increased risk of cardiovascular incidents, adult hypertension and diabetes. Preterm-born children and those with fetal growth restriction (FGR) who demonstrate rapid changes in their weight percentile should remain under surveillance with blood pressure monitoring. A better understanding of lifelong health outcomes of preterm-born individuals is crucial for developing strategies to prevent cardiovascular sequelae and may be the basis for future research to provide effective interventions.

Clinical presentation of 13 children with alkaptonuria.

Until now, only a few studies have focused on the early onset of symptoms of alkaptonuria (AKU) in the pediatric population. This prospective, longitudinal study is a comprehensive approach to the assessment of children with recognized AKU during childhood. The study includes data from 32 visits of 13 patients (five males, eight females; age 4-17 years) with AKU. A clinical evaluation was performed with particular attention to eye, ear, and skin pigmentation, musculoskeletal complaints, magnetic resonance imaging (MRI), and ultrasound (US) imaging abnormalities. The cognitive functioning and adaptive abilities were examined. Molecular genetic analyses were performed. The most common symptoms observed were dark urine (13/13), followed by joint pain (6/13), and dark ear wax (6/13). In 4 of 13 patients the values obtained in the KOOS-child questionnaire were below the reference values. MRI and US did not show degenerative changes in knee cartilages. One child had nephrolithiasis. Almost half of the children with AKU (5/13) presented deficits in cognitive functioning and/or adaptive abilities. The most frequent HGD variants observed in the patients were c.481G>A (p.Gly161Arg) mutation and the c.240A>T (p.His80Gln) polymorphism. The newly described allele of the HGD gene (c.948G>T, p.Val316Phe) which is potentially pathogenic was identified.

The Epidermal Transcriptome Analysis of a Novel c.639_642dup LORICRIN Variant-Delineation of the Loricrin Keratoderma Pathology.

Loricrin keratoderma (LK) is a rare autosomal dominant genodermatosis caused by LORICRIN gene mutations. The pathogenesis of the disease is not yet fully understood. So far, only 10 pathogenic variants in LORICRIN have been described, with all of them but one being deletions or insertions. The significance of rare nonsense variants remains unclear. Furthermore, no data regarding the RNA expression in affected patients are available. The aim of this study is to describe the two variants in the LORICRIN gene found in two distinct families: the novel pathogenic variant c.639_642dup and a rare c.10C > T (p.Gln4Ter) of unknown significance. We also present the results of the transcriptome analysis of the lesional loricrin keratoderma epidermis of a patient with c.639_642dup. We show that in the LK lesion, the genes associated with epidermis development and keratocyte differentiation are upregulated, while genes engaged in cell adhesion, differentiation developmental processes, ion homeostasis and transport, signaling and cell communication are downregulated. In the context of the p.Gln4Ter clinical significance evaluation, we provide data indicating that LORICRIN haploinsufficiency has no skin consequences. Our results give further insight into the pathogenesis of LK, which may have therapeutic implications in the future and important significance in the context of genetic counseling.

Diagnosis and Management of Mucopolysaccharidosis Type II (Hunter Syndrome) in Poland.

Mucopolysaccharidosis type II (MPS II; also known as Hunter syndrome) is a rare, inherited lysosomal storage disease. The disease is caused by deficiency of the lysosomal enzyme iduronate-2-sulphatase (I2S) due to mutations in the IDS gene, which leads to accumulation of glycosaminoglycans (GAGs). Deficiency of I2S enzyme activity in patients with MPS II leads to progressive lysosomal storage of GAGs in the liver, spleen, heart, bones, joints, and respiratory tract. This process disturbs cellular functioning and leads to multisystemic disease manifestations. Symptoms and their time of onset differ among patients. Diagnosis of MPS II involves assessment of clinical features, biochemical parameters, and molecular characteristics. Life-long enzyme replacement therapy with idursulfase (recombinant human I2S) is the current standard of care. However, an interdisciplinary team of specialists is required to monitor and assess the patient's condition to ensure optimal care. An increasing number of patients with this rare disease reach adulthood and old age. The transition from pediatric care to the adult healthcare system should be planned and carried out according to guidelines to ensure maximum benefit for the patient.

Contributors to Preterm Birth: Data from a Single Polish Perinatal Center.

Preterm birth may result from overlapping causes including maternal age, health, previous obstetric history and a variety of social factors. We aimed to identify factors contributing to preterm birth in respect to new social and environmental changes in the reproductive patterns. Our cross-sectional study included 495 mother-infant pairs and was based on maternal self-reporting in an originally developed questionnaire. Neonates were divided into two groups: 72 premature babies (study group) and 423 full-term babies (control group). We analyzed maternal, sociodemographic and economic characteristics, habits, chronic diseases, previous obstetric history and pregnancy complications. For statistical analysis, Pearson's Chi-squared independence test was used with a statistical significance level of 0.05. Preterm births were more common among mothers living in villages (p < 0.001) and with lower education level (p = 0.01). Premature births were also positively associated with mothers who were running their own businesses (p = 0.031). Mothers with a history of previous miscarriages gave birth at a significantly older age (p < 0.001). The most frequent pregnancy complications were hypothyroidism (41.4%), pregestational and gestational diabetes mellitus (DM; 17.8%) and hypertension (8.1%). Pregestational DM significantly influenced the occurrence of prematurity (p < 0.05). Pregestational DM, being professionally active, a lower education level and living outside cities are important risk factors of prematurity.

Lipid Profile, Lp(a) Levels, and HDL Quality in Adolescents with Down Syndrome.

The improvement in the lifespan of individuals with Down syndrome (DS) has created interest in the context of the development of age-related diseases. Among them is atherosclerosis-based cardiovascular disease (CVD), which seems to be an especially urgent and important issue. The aim of the present study was to evaluate the lipid markers that may clarify cardiovascular risk profiles in individuals with DS. To this end, we analyzed lipid profile parameters, including lipoprotein(a) (Lp(a)) levels, protein composition, and the antioxidative properties of high-density lipoprotein (HDL), in 47 adolescents with DS and 47 individuals without DS. Compared with the control group (C), subjects with DS had significantly increased concentrations of low-density lipoprotein cholesterol (105 ± 31 vs. 90 ± 24 mg/dL, p = 0.014), non-high-density lipoprotein cholesterol (120 ± 32 vs. 103 ± 26 mg/dL, p = 0.006), and triglycerides (72 [55−97] vs. 60 [50−77] mg/dL, p = 0.048). We found that patients with DS were characterized by significantly higher Lp(a) levels (31.9 [21.5−54.3] vs. 5.2 (2.4−16.1) mg/dL, p < 0.001). In fact, 57% of individuals with DS had Lp(a) levels above 30 mg/dL, which was approximately four times higher than those in the control group (DS 57% vs. C 15%). Apart from decreased high-density lipoprotein cholesterol levels in the subjects with DS (53 ± 11 vs. 63 ± 12 mg/dL, p < 0.001), differences in parameters showing the quality of HDL particles were observed. The concentrations of the main proteins characterizing the HDL fraction, apolipoprotein A-I and apolipoprotein A-II, were significantly lower in the DS group (144 ± 21 vs. 181 ± 33 mg/dL, p < 0.001; 33 ± 6 vs. 39 ± 6 mg/dL, p < 0.001, respectively). No significant differences between the groups were observed for the concentration of paraoxonase-1 (DS 779 ± 171 vs. C 657 ± 340 ng/mL, p = 0.063), enzyme activities toward paraoxon (DS 219 [129−286] vs. C 168 [114−272] IU/L, p = 0.949), or phenyl acetate (DS 101 ± 20 vs. C 93 ± 21 kIU/L, p = 0.068). There were no differences in myeloperoxidase activity between the study groups (DS 327 [300−534] vs. C 426 [358−533] ng/mL, p = 0.272). Our results are the first to demonstrate an unfavorable lipid profile combined with higher Lp(a) levels and quality changes in HDL particles in individuals with DS. This sheds new light on cardiovascular risk and traditional healthcare planning for adolescents with DS.

SHFLD3 phenotypes caused by 17p13.3 triplication/ duplication encompassing Fingerin (BHLHA9) invariably.

BACKGROUND: Split-hand/ foot malformation with long bone deficiency 3 (SHFLD3) is an extremely rare condition associated with duplications located on 17p13.3, which invariably encompasses the BHLHA9 gene. The disease inherits with variable expressivity and significant incomplete penetrance as high as 50%. RESULTS: We have detected 17p13.3 locus one-allele triplication in a male proband from family 1 (F1.1), and duplication in a male proband from family 2 (F2.1) applying array comparative genomic hybridization (array CGH). The rearrangements mapped to the following chromosomal regions-arr[GRCh38] 17p13.3(960254-1291856)×4 in F1.1 and arr[GRCh38] 17p13.3(1227482-1302716)×3 in F2.1. The targeted quantitative PCR revealed that the 17p13.3 locus was also duplicated in the second affected member from family 2 (F2.2; brother of F2.1). In the next step, we performed segregation studies using quantitative PCR and revealed that F1.1 inherited the triplication from his healthy father-F1.2, whereas the locus was unremarkable in the mother of F2.1 & F2.2 and the healthy son of F2.1. However, the duplication was present in a healthy daughter of F2.2, an asymptomatic carrier. The breakpoint analysis allowed to define the exact size and span of the duplicated region in Family 2, i.e., 78,948 bp chr17:1225063-1304010 (HG38). Interestingly, all symptomatic carriers from both families presented with variable SHFLD3 phenotype. The involvement of secondary modifying locus could not be excluded, however, the Sanger sequencing screening of BHLHA9 entire coding sequence was unremarkable for both families. CONCLUSIONS: We have shed light on the one-allele CNV triplication occurrence that should be considered when a higher probe (over duplication range) signal is noted. Second, all SHFLD3 patients were accurately described regarding infrequent limb phenotypes, which were highly variable even when familial. Of note, all symptomatic individuals were males. SHFLD3 still remains a mysterious ultra-rare disease and our findings do not answer crucial questions regarding the disease low penetrance, variable expression and heterogeneity. However, we have presented some clinical and molecular aspects that may be helpful in daily diagnostic routine, both dysmorphological and molecular assessment, of patients affected with SHFLD3.

Analysis of Dietary Habits and Nutritional Status of Children with Down Syndrome in the Context of Lipid and Oxidative Stress Parameters.

Introduction: The risk of obesity in children with Down syndrome is high. Undoubtedly, proper nutrition plays an important role in the prevention of excess body weight and is associated with a reduction of metabolic complications. The aim of the study was to assess the problem of disturbances in the nutritional status and eating habits of children with DS. Methods: A total of 39 patients were included in the study. The nutritional status was assessed by anthropometric tests and Dual X-ray Absorptiometry. Eating habits were assessed using the Child Eating Behavior Questionnaire and the Food Frequency Questionnaire. Blood samples were taken to determine the oxidative stress and lipid parameters. Results: Obesity was recognized in 15% of subjects and 23% were overweight. Children that were overweight were characterized by higher levels of triglycerides, atherogenic index of plasma, and apoA2 and apoE levels. Fat mass, fat mass/height2 index, and visceral fat mass correlated with thiobarbituric acid reactive substances and advanced oxidative protein product level. The analysis of the Child Eating Behavior Questionnaire showed that children struggling with being overweight were more interested in food compared to those with normal body weight. A positive correlation was identified between waist circumference and food interest categories. Insufficient consumption of dairy products, vegetables, whole grain products, as well as fruits, seeds, nuts, and fatty fish was noted. Patients were less likely to consume products that are a good source of mono- and polyunsaturated fatty acids. Conclusions: In children with Down syndrome and obesity, disturbances in lipid and oxidative stress parameters are observed. Abnormal eating habits in all children with Down syndrome regardless of their nutritional status were noted. Proper nutritional education, nutritional control, and management of metabolic problems are essential in this group of patients.

Highly diverse phenotypes of mucopolysaccharidosis type IIIB sibling patients: effects of an additional mutation in the AUTS2 gene.

Mucopolysaccharidosis type IIIB (MPS IIIB or Sanfilippo syndrome type B) is an inherited metabolic disease caused by mutations in the NAGLU gene, encoding α-N-acetylglucosaminidase. Accumulation of undegraded heparan sulfate (one of glycosaminoglycans) arises from deficiency in this enzyme and leads to severe symptoms, especially related to dysfunctions of the central nervous system. Here, we describe a case of two siblings with highly diverse phenotypes, despite carrying the same mutations (c.1189 T > G/c.1211G > A (p.Phe397Val/p.Trp404Ter)) and similar residual activities of α-N-acetylglucosaminidase; the younger patient reveals more severe phenotype; thus, these differences cannot be explained by the age and progression of the disease. Surprisingly, the whole exome sequencing analysis indicated the presence of an additional mutation in one allele of the AUTS2 gene (c.157G > A (p.Ala53Thr)) in the younger patient but not in the older one. Since mutations in this gene are usually dominant and cause delayed development and intellectual disability, it is likely that the observed differences between the MPS IIIB siblings are due to the potentially pathogenic AUTS2 variant, present in one of them. This case confirms also that simultaneous occurrence of two ultra-rare diseases in one patient is actual, despite a low probability of such a combination. Moreover, it is worth noting that apart from the genotype-phenotype correlation and the importance of the residual activity of the deficient enzyme, efficiency of glycosaminoglycan synthesis and global secondary changes in expression of hundreds of genes may considerably modulate the course and severity of MPS, especially Sanfilippo disease.

Relationship between growth and intelligence quotient in children with Down syndrome.

Background: The relationship between intelligence quotient (IQ) and somatic development, especially growth, has been demonstrated in various groups of children. Down syndrome (DS) is characterized by short stature, overweight, and cognitive impairment. The objective of our work was to assess whether anthropometric measurements [weight, height, body mass index (BMI)] of children with DS correlate with their IQ. The results of the study may be valuable for this population in the light of increasing access to growth hormone therapy (GHT) in various genetic syndromes with short stature. Based on previous studies on children, we hypothesized that a link exists between IQ and somatic development, particularly growth. Methods: This cross-sectional study included 40 children with DS, who were aged 9-18 years. The studied population was selected from the registry of the Genetic Clinic at the University Clinical Center in Gdansk (Poland). Anthropometric measurements (weight and height) were taken for all the children, and their BMI was determined using these data. The obtained results were plotted on charts for children with DS. The IQ of the children was assessed using the Stanford Binet Intelligence Scale, Fifth Edition. The correlations between IQ and anthropometric data were analyzed using univariate correlation and multiple regression analyses. Results: The results showed that full-scale, verbal, and nonverbal IQ correlated with height percentile (P=0.03, P=0.02, and P=0.04, respectively), but not with weight (P=0.26, P=0.19, and P=0.61, respectively) or BMI (P=0.6, P=0.5, and P=0.72, respectively). In multiple linear regression analysis, height percentile remained as an independent determinant of the IQ results after adjusting for birth weight, hypothyroidism with L-thyroxine replacement therapy, and congenital cardiac defect (ß=0.48, P=0.018). Conclusions: The results of our study suggest an association between growth and IQ in children with DS. The presented findings may be valuable for improving access to GHT for populations with genetic syndromes characterized by short stature. However, these should be confirmed by further research with a longitudinal sample of children with DS.

Factors affecting the prevalence of overweight and obesity in children with Down Syndrome.

BACKGROUND: The aim of this study was to determine the influence of environmental factors on the occurrence of overweight and obesity in children with Down syndrome. METHODS: The study was conducted in a group of children with Down Syndrome under the care of the Genetic Clinic in Gdansk from May 2017 to December 2018. RESULTS: The study included 26 female patients and 22 male patients with Down Syndrome, aged 7 to 18 years. The children were divided into two groups: group 1, with normal body weight and underweight; and group 2, with obesity and overweight. Overweight and obesity were diagnosed in 19% of children with Down Syndrome. The BMI analysis of the parents showed that the fathers of children with obesity and overweight had a higher BMI (P=0.043). In the group of children with overweight and obesity, obesity was more common in siblings (P=0.029), and sucking disorders were less frequent in the infancy period (P=0.015). Children with obesity and overweight were more likely to eat white bread (P=0.039), milk and other dairy products (P=0.04), and eggs (P=0.029) and ate more often between meals (P=0.022). CONCLUSIONS: In families of children with Down Syndrome affected by overweight and obesity, nutritional disorders were more frequent in the other members of the family. More frequent unhealthy dietary choices were found in children with Down Syndrome affected by overweight and obesity than in children with a normal body weight and underweight. It is necessary to educate families about the principles of a healthy lifestyle, as it can improve the quality of life of patients with Down syndrome and the whole family.

Immune Dysregulation in Patients With Chromosome 18q Deletions-Searching for Putative Loci for Autoimmunity and Immunodeficiency.

Introduction: Autoimmune disorders, IgA deficiency, and allergies seem to be common among individuals with 18q deletion syndrome [OMIM 601808]. We aimed to determine the prevalence, mechanism, and genetic background of autoimmunity, immune deficiency, and allergy in a cohort of patients with 18q deletions. Material and Methods: Medical registries and social media were used to recruit the patients. Microarray oligonucleotide comparative genomic hybridization (aCGH) (Agilent, Santa Clara, CA, USA) was performed in all patients to identify size and location of chromosome 18 deletion. Clinical evaluation and medical record collection were performed in each of the study participants. The history of autoimmune disorders, severe and/or recurrent infections, and symptoms of allergy were noted. Total immunoglobulin IgG, IgA, IgM, IgE, and IgG1-4 serum levels were measured using nephelometry and ELISA methods. Lymphocyte T subset phenotyping was performed in 24 subjects from 18q del cohort. To predict the most promising candidate genes, we used the ENDEAVOUR-a free web resource for gene prioritization. Results: 18q deletion was confirmed by means of array CGH analysis in 27 individuals, 15 (55.6%) females and 12 males, referred to the project by specialists in medical genetics, diabetology, or pediatric endocrinology between May 2015 and December 2019. The mean age at examination was 11.8 years (min-max: 4.0-33.5). Autoimmune disorders were present in 14/27 (51.8%) of the cohort. In eight of patients, symptoms of immune deficiency coexisted with autoimmunity. Allergy was reported in nine of 27 (33.4%) patients. Over 89% of patients presented with at list one type of immunoglobulin (IgA, IgM, IgG, IgE, and IgG1-4) deficiency and eight of 25 (32%) had abnormalities in at least two major immunoglobulin (IgG, IgA, IgM) measurements (CVID-like phenotype). Patients with 18q del exhibited a significantly decreased CD4, Treg FOXP3+, TregFOXP3+Helios+, and TemCD4 cell numbers in comparison with the control groups of 24 T1DM patients and 28 healthy controls. Conclusions: Patients with 18q deletions frequently suffer from autoimmune disorders, recurrent infections, and allergy due to immune dysregulation presenting with variable antibody deficiencies and T-regulatory cell deficiency (CD4+CD25+CD127lowFOXP3+). The spectrum of speculations regarding which gene might be responsible for such phenotype ranges from single gene haploinsufficiency to deletion of a cluster of immunogenes located distally to 18q21.

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's 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.

Syndromic neurodevelopmental disorder associated with de novo variants in DDX23.

The DEAD/DEAH box RNA helicases are a superfamily of proteins involved in the processing and transportation of RNA within the cell. A growing literature supports this family of proteins as contributing to various types of human disorders from neurodevelopmental disorders to syndromes with multiple congenital anomalies. This article presents a cohort of nine unrelated individuals with de novo missense alterations in DDX23 (Dead-Box Helicase 23). The gene is ubiquitously expressed and functions in RNA splicing, maintenance of genome stability, and the sensing of double-stranded RNA. Our cohort of patients, gathered through GeneMatcher, exhibited features including tone abnormalities, global developmental delay, facial dysmorphism, autism spectrum disorder, and seizures. Additionally, there were a variety of other findings in the skeletal, renal, ocular, and cardiac systems. The missense alterations all occurred within a highly conserved RecA-like domain of the protein, and are located within or proximal to the DEAD box sequence. The individuals presented in this article provide evidence of a syndrome related to alterations in DDX23 characterized predominantly by atypical neurodevelopment.

Clinical characteristics of Polish patients with molecularly confirmed Mowat-Wilson syndrome.

Mowat-Wilson syndrome is a rare neurodevelopmental disorder caused by pathogenic variants in the ZEB2 gene, intragenic deletions of the ZEB2 gene, and microdeletions in the critical chromosomal region 2q22-23, where the ZEB2 gene is located. Mowat-Wilson syndrome is characterized by typical facial features that change with the age, severe developmental delay with intellectual disability, and multiple congenital abnormalities. The authors describe the clinical and genetic aspects of 28th patients with Mowat-Wilson syndrome diagnosed in Poland. Characteristic dysmorphic features, psychomotor retardation, intellectual disability, and congenital anomalies were present in all cases. The incidence of most common congenital anomalies (heart defect, Hirschsprung disease, brain defects) was similar to presented in literature. Epilepsy was less common compared to previously reported cases. Although the spectrum of disorders in patients with Mowat-Wilson syndrome is wide, knowledge of characteristic dysmorphic features awareness of accompanying abnormalities, especially intellectual disability, improves detection of the syndrome.