Carrier Mothers Research Articles

Investigate the Presence of HBV Surface Antigen in Pregnant Women, Cairo City in Egypt.

Hepatitis means inflammation of the liver, and hepatitis B is a common and dangerous liver disease caused by the Hepatitis B Virus (HBV) of the DNA hepadnavirus family. In 2010, the World Health Organization (WHO) considered hepatitis B infection a major health problem worldwide. One way of transmitting this disease is a transmission from a carrier mother to a child. This study aimed to investigate the presence of HBV surface antigen in pregnant women referred to Kasra Al-Aini Hospital in Cairo. This study was a cross-sectional descriptive study that was performed on pregnant women. One thousand pregnant women were selected with their consent to participate in this study, and after preparing a blood sample, an Enzyme-linked Immunosorbent Assay kit, used for Hepatitis B Virus surface antigen detection, a questionnaire containing questions about socio-individual characteristics. Among 1000 samples, 13 samples were equal to 1.3% had HBsAg positive. No significant relationship was found between the prevalence of HBs Ag in the city and rural location, education, occupation, age, and history of abortion in pregnant women. History of dialysis in pregnant women, tattooing, and type of job of the pregnant woman was not considered risk factors. However, injection drug users, history of previous surgery, and blood transfusion can be considered suspicious factors (P≤0.05). The prevalence of hepatitis B infection in pregnant women in Cairo was 1.3, which is lower than the study statistics in most parts of the world. However, to evaluate this amount more accurately, there is a need to conduct a study with a higher sample size.

Severe Phenotype in Patients with X-linked Hydrocephalus Caused by a Missense Mutation in L1CAM.

Objective:The study aimed to show the clinical characteristics and prognosis of the L1 syndrome in patients with L1CAM mutations in the extracellular region.Materials and Methods:Three affected boys and their siblings and parents from a large family were included in this study. Genetic etiology was investigated by whole-exome sequencing in the index patient. The pathogenic variant was detected by whole-exome sequencing and was validated by Sanger sequencing in 3 patients and other family members.Results:We present 2 brothers and their cousin with prenatal onset hydrocephalus, severe developmental and speech delay, corpus callosum agenesis/hypogenesis, epilepsia, and adducted thumbs. A hemizygous missense mutation NM_024003 (c.A2351G:p.Y784C) on exon 18 of L1CAM gene was found in the 3 patients and their carrier mother. This missense mutation in the conserved region of the second fibronectin type III-like repeats located in the extracellular region of L1CAM resulted in the severe phenotype of X-linked inherited L1 syndrome in the patients.Conclusion:L1 syndrome should be considered in the differential diagnosis of male children with intellectual disability, hydrocephalus, and adducted thumbs. While truncating mutations of L1CAM may cause a more severe phenotype, missense mutations cause milder forms. However, pathogenic missense mutations affecting key amino acid residues lead to severe phenotype likely.

Acquired Hemophilia A in a Female: A Case Report

INTRODUCTION: Coagulation factor deficit is a very uncommon hemostatic condition in which a single component or numerous factors are lacking. Hereditary coagulation factor defects are autosomal recessive, meaning that they can affect both men and women. However, hemophilia A, caused by lack of clotting factor VIII (FVIII), is an X-linked condition. Acquired hemophilia A (AHA) is a bleeding disorder caused by autoantibodies to FVIII. It should be distinguished from congenital hemophilia, an inherited disorder caused by a mutation in the FVIII gene. Here, we report the first known case in Indonesia, a 24-year-old female diagnosed with AHA. CASE PRESENTATION: A 24-year-old woman was referred to our facility for prolonged epistaxis. She had no previous history of extended menstrual flow or frequent epistaxis episodes, and there was no history of epistaxis or prolonged bleeding in her family. Bleeding time and prothrombin time were both normal, but time to activate partial thromboplastin was longer. The patient was diagnosed with AHA after von Willebrand disease (VWD) was ruled out. DISCUSSION: In some rare situations, females can be affected by X-linked illnesses such as hemophilia A and B. This may be due to a carrier mother or affected father, skewed X chromosome inactivation, Turner syndrome, inhibitory antibodies (acquired hemophilia), or a random mutation on the active X chromosome. In such instances, treatment is challenging. The usual treatment of choice is recombinant coagulation factors. CONCLUSION: Although VWD is the most frequent hereditary bleeding problem in females, other rare disorders such as AHA may be implicated. Clinicians should be aware of this when faced with patients that lack a history of bleeding disorders. Furthermore, AHA should be considered as a differential diagnosis in every female patient suffering from hemorrhage. Therefore, a comprehensive diagnostic approach is needed.

Efficacy of the hepatitis B vaccine alone in the prevention of hepatitis B perinatal transmission in infants born to hepatitis B e antigen-negative carrier mothers

BackgroundVertical mother-to-child transmission (MTCT) of the hepatitis B virus (HBV) remains an important issue. Timely administration of hepatitis B immunoglobulin (HBIG) and of the HBV vaccine is effective in preventing MTCT in infants born to HBV-infected mothers. However, HBIG is often not easily available in low-income countries or regions. MethodsWe compared in a retrospective cohort study the HBV vaccine efficacy alone and in combination with HBIG in preventing vertical MTCT in infants born to HBeAg-negative carrier mothers in Jiangsu province, China. Based on the administration of the HBV vaccine and HBIG shortly after birth, children were divided into two groups: Group 1, administration of the HBV vaccine alone, and Group 2, concurrent use of HBIG and of the HBV vaccine. ResultsA total of 620 infants born to HBeAg-negative carrier mothers were enrolled into this study. Group 1 included 195 children who had received the HBV vaccine alone after birth, and Group 2, 425 children who had received both HBIG and the HBV vaccine. Children were followed up to the age of 68 and 42 months, respectively. MTCT of HBV occurred in 0% (0/195) in Group 1 (HBV vaccine alone) and 0% (0/425) in Group 2 (HBV vaccine and HBIG) (p = 1.00). ConclusionIn this retrospective cohort study, we found that HBV vaccination alone shortly after birth was effective in preventing MTCT of HBV in infants born to HBeAg-negative carrier mothers.

Change in Maladaptive Behavior Affects Intergenerational Relationships in Fragile X Syndrome.

This study investigated the bidirectional effects of change in maladaptive behaviors among adolescents and adults with fragile X syndrome (FXS) and change in their intergenerational family relationships over a 7.5-year period. Indicators of the intergenerational family relationship between premutation carrier mothers and their adolescent or adult son/daughter with FXS included a measure of the quality of the relationship, as well as descriptions provided by mothers of their relationship with their son/daughter (positive remarks, critical remarks). Maladaptive behaviors decreased, maternal positive remarks increased, and maternal critical remarks and relationship quality remained stable over time. Bidirectional effects of change were observed in predicting maladaptive behaviors and maternal positive remarks, although maladaptive behaviors more strongly predicted positive remarks than the reciprocal association. This research suggests prioritizing maladaptive behaviors in the context of family interventions.

Identification of a Hemizygous Novel Splicing Variant in ATRX Gene: A Case Report and Literature Review.

BackgroundAlpha-thalassemia/intellectual disability syndrome (ATR-X) (OMIM # 301040) was first described by Wilkie et al. (1). Several studies found that children who presented with significantly consistent clinical phenotypes of hemoglobin H (Hb H) disease and profound mental handicap carried ATRX chromatin remodeler (ATRX, OMIM*300032) gene variants. With the recent development of exome sequencing (ES), ATRX gene variants of severe to profound intellectual disability without alpha-thalassemia have been implicated in intellectual disability-hypotonic facies syndrome, X-linked, 1(MRXHF1, OMIM #309580). These two diseases present similar clinical manifestations and the same pattern of inheritance.Case PresentationWe reported a 3-year-old boy with intellectual disability, language impairment, hypotonia, and mild craniofacial abnormalities (flat nasal bridge, small and triangular nose, anteverted nostrils, and widely spaced incisors) and reviewed MRXHF1 cases. At an early stage, the patient developed global developmental delay (GDD). After 6 months of rehabilitation therapy, the patient's motor ability did not make big progress, as well as his speech or nonverbal communication. We performed whole-genome sequencing (WGS), Sanger sequencing, reverse transcription-polymerase chain reaction (RT-PCR), and X-inactivation studies. A novel hemizygous intronic variant in ATRX (c.5786+4A>G; NM_000489.6) was identified, which led to exon 24 skipping. The carrier mother showed extremely skewed X-chromosome inactivation (XCI). These results may contribute to the patient's phenotypes.ConclusionsThe novel hemizygous intronic variant in ATRX is the genetic etiology of the boy. Identification of this variant is helpful for parents to take prenatal diagnostic tests. Also, this new case expands the phenotypes of MRXHF1 and the mutational spectrum of the ATRX gene.

Identification of a novel MAGT1 mutation supports a diagnosis of XMEN disease

XMEN (X-linked immunodeficiency with magnesium defect) is caused by loss-of-function mutations in MAGT1 which is encoded on the X chromosome. The disorder is characterised by CD4 lymphopenia, severe chronic viral infections and defective T-lymphocyte activation. XMEN patients are susceptible to Epstein-Barr virus infections and persistently low levels of intracellular Mg2+. Here we describe a patient that presented with multiple recurrent infections and a subsequent diffuse B-cell lymphoma. Molecular genetic analysis by exome sequencing identified a novel hemizygous MAGT1 nonsense mutation c.1005T>A (NM_032121.5) p.(Cys335*), confirming a diagnosis of XMEN deficiency. Follow-up immunophenotyping was performed by antibody staining and flow cytometry; proliferation was determined by 3H-thymidine uptake after activation by PHA and anti-CD3. Cytotoxic natural killer cell activity was assessed with K562 target cells using the NKTESTTM assay. While lymphocyte populations were superficially intact, B cells were largely naive with a reduced memory cell compartment. Translated NKG2D was absent on both NK and T cells in the proband, and normally expressed in the carrier mother. In vitro NK cell activity was intact in both the proband and his mother. This report adds to the growing number of identified XMEN cases, raising awareness of a, still rare, X-linked immunodeficiency.

EP296: Familial MECP2 variants: a report of 4 affected families highlighting the variable phenotypic spectrum and implications for genetic counseling

Pathogenic variants in MECP2 cause a spectrum of neurodevelopmental disorders, most commonly Rett syndrome (RTT; 312750). Although historically this was considered an X-linked dominant diagnosis with male lethality, it is now known that males can also be affected, with a disease spectrum ranging from severe neonatal encephalopathy to intellectual disability (ID). Other features commonly seen in RTT are inconsistently present in males. A qualified genotype-phenotype correlation exists, with variants that are known to cause RTT in females most often leading to more severe phenotypes in males. Additionally, whereas pathogenic MECP2 variants identified in affected females with classic and atypical RTT are most often de novo variants, pathogenic variants in males may be either de novo or maternally inherited. Here we report 4 novel families with pathogenic MECP2 variants. In all 4 families, the affected probands were male and maternal inheritance was identified. Family 1: The proband is a now 8-year-old male with mild global developmental delay, epilepsy, ataxia, and hypotonia. He also has significant anxiety. Epilepsy gene panel identified a hemizygous pathogenic variant in MECP2 (c.491C>T; p.Ala140Val); targeted testing confirmed maternal inheritance. His mother has no significant medical issues or learning issues, but endorses a history of anxiety. He has four clinically unaffected siblings; one brother has been tested and is negative. His other brother and sisters have not been tested. Family 2: The proband is a now 47-year-old male with mild-moderate intellectual disability. Genetic testing was initiated after MRI performed in the context an episode of confusion and shaking concerning for a panic attack revealed signal abnormalities in the bilateral cerebral peduncles possibly concerning for Fragile X Associated Tremor Ataxia Syndrome (FXTAS). He also experienced a motor regression and onset of dystonia after an episode of rhabdomyolysis in his mid 40’s and has not returned to baseline. Trio exome sequencing identified a maternally inherited hemizygous pathogenic variant (c.499C>T; p.Arg167Trp) in MECP2. Cascade testing identified that his sister and niece also both carry the familial MECP2 variant. His sister has a history of learning difficulties, significant anxiety, obsessive compulsive disorder, and has developed progressive spasticity with hyperreflexia and sustained clonus over time. His niece also has anxiety, obsessive compulsive disorder, and bipolar disorder. Family 3: The proband is a now 37-year-old male with mild intellectual disability and autism spectrum disorder. He also has a history of anxiety and depression. Trio exome sequencing identified a maternally inherited hemizygous pathogenic variant (c. 1136_1151del16; p.Pro379HfsX25) in MECP2. Testing was initiated after the onset of abnormal movements in his thirties suggestive of dystonia. Exam was notable for kyphosis and shuffling gait. His mother reports a history of anxiety, but no learning or cognitive concerns and no other neurologic symptoms. He has one clinically unaffected sister who has not yet been tested. Exome sequencing also identified a de novo, heterozygous c.1672C>T (p.Arg558Cys) variant of uncertain significance in ALDH18A1, though it is unclear whether or not this is contributing to his phenotype. Family 4: The proband is a now 8-year-old male who initially presented for evaluation due to concern for global developmental delay, hypotonia, and macrocephaly. Family history was unremarkable. MRI identified prominent perivascular spaces. Trio exome sequencing identified a maternally inherited likely pathogenic hemizygous variant (c.1244delC; p.Pro415LeufsX6) in MECP2. The proband’s younger brother subsequently presented with expressive language delay and was also macrocephalic. Targeted testing confirmed the presence of the familial MECP2 variant. These 4 familial reports of pathogenic MECP2 variants add to the data provided by previous publications describing the phenotypic spectrum in affected males and supporting that many of the variants may be maternally inherited. Affected male probands in all cases presented with developmental delay and/or intellectual disability. Only 1/4 probands had epilepsy. Anxiety was present in 3/4. Cascade testing identified carrier female relatives with a prominent neuropsychiatric phenotype in one family. Anxiety was also reported in the mothers of two other families, without any other cognitive or neurologic features. Although two families harbored pathogenic missense variants previously known to be associated with an X-linked intellectual disability phenotype, two families with mildly affected male probands and unaffected female carrier mothers had novel, predicted loss of function variants that would have been expected to result in a RTT phenotype. These families highlight the clinical variability that can be seen with pathogenic MECP2 variants and challenge reported genotype-phenotype correlations, providing important information for genetic counseling.

Vertical Transmission of HIV-HBV Co-infection with Liquor Habit and Vaccination

In this paper, the transmission of HIV-HBV co-infection is carried out. The individuals who are infected with both diseases HIV and HBV simultaneously, are said to be HIV-HBV co-infected. These infected individuals have high risk of liver failure. It is the main cause for serious liver complications like cirrhosis and liver cancer at younger age. A deterministic model is considered with liquor habit in men and vaccination to new-borns and carrier mother. Carrier class results in the vertical transmission. In this paper, the transmission dynamics of the model is analyzed. The total population is divided in to twenty eight class viz. Susceptible, HBV Vaccinated, HBV-infected female, HBV-carrier female, HBV infected alcoholic male, HBV carrier alcoholic male, HBV infected non-alcoholic male, HBV carrier non-alcoholic male, HBV recovered class, pre-AIDS female, AIDS female, pre-AIDS-HBV co-infected female, AIDS-HBV co-infected female, pre-AIDS-HBV carrier female, AIDS-HBV carrier female, pre-AIDS alcoholic male, AIDS alcoholic male, pre-AIDS non-alcoholic male, AIDS non-alcoholic male, pre-AIDS-HBV co-infected alcoholic male, pre-AIDS-HBV co-infected non-alcoholic male, pre-AIDS-HBV carrier alcoholic male, pre-AIDS-HBV carrier non-alcoholic male, AIDS-HBV co-infected alcoholic male, AIDS-HBV co-infected non-alcoholic male, AIDS-HBV carrier non-alcoholic male, HIV infected -HBV recovered classes. The basic reproduction numbers for HIV, for HBV and for HIV-HBV are found using next generation matrix. Local and global stability of HIV-HBV disease free equilibrium is worked out. Model is validated with the numerical simulation.

Different patterns of autofluorescence within the same family in carriers of a novel choroideremia mutation

AbstractPurposeChoroideremia (CHM) is a rare retinal dystrophy. It affects both the retina (retinal pigment epithelium (RPE) and outer retina) and the choroidal layers. It is inherited X‐linked and therefore affects all males with a theoretical penetrance of 100%. Female carriers, due to the phenomenon of lionisation may be asymptomatic or suffer from the disease in a similar way to males. On examination, they may have changes in pigment distribution and autofluorescence (AF) changes. They may also have some degree of retinal dysfunction.MethodsWe report a family with two cousins affected by CHM and their carrier mothers. After the diagnosis of an 11‐year‐old male, a complete ophthalmological examination including optical coherence tomography (OCT), microperimetry (MAIA) and AF was performed on all family members. A genetic study was conducted on those cases suggestive of CHM. One other case (a 10‐year‐old cousin) and two carriers, the mothers of the two confirmed cases, were identified. The sisters were not affected.ResultsAll four showed an undescribed mutation in the CHM gene c.1083_1084dupT (p.L362Sfs*56) at location Xp21.2. AF findings were different in both carriers, with a fine speckle pattern on the periphery in one of them and a course and geographic pattern shown low‐density peripapillary pattern and coarse mottled on periphery in the other one. Both affected males showed a clear decrease in the AF pattern with a geographic central persistence (male pattern). During the evolution, one of the patients showed a more aggressive form than the other, which could be justified by the concomitant high myopia in this case. The AF of the carriers remained similar.ConclusionsConsidering that AF is a non‐invasive, fast and accessible test, could serve to diagnose both patients and carriers of CHM. In addition, the pattern of AF in carriers may be different in members of the same family despite having the same mutation.

Hemophilia: The Past, the Present, and the Future.

Hemophilia: The Past, the Present, and the Future.

Anti-HBs levels in children under the age of two years born to HBV carrier mothers after immunoprophylaxis: a multicenter cross-sectional study

BackgroundSerological testing for the presence of Hepatitis B Virus (HBV) markers and anti-HBs titers in infants born to HBsAg positive women is critically important for estimation in immunisation programme.MethodsThis was a multi-center and cross-sectional study conducted in Zhejiang province, China. Children aged 7 to 24 months born to HBsAg positive women during December 2018 to February 2019, completed additional HBV serological markers screening. We indicated distribution of HBV serological markers and anti-HBs titers in children. Multiple logistic regression model with adjusted odds ratio and 95% confidence interval (ORadj and 95% CI) was used to explore the factors associated with inadequate immune response (anti-HBs titers< 100 mIU/ml) among children.ResultsA total of 1849 children were included. Overall 25 children tested HBsAg positive, giving HBsAg positive rate of 1.35%(95%CI: 0.83-1.88%). 92.00% (23/25) HBsAg positive children were delivered by HBeAg positive mothers. The proportion of protective seroconversion (anti-HBs titers≥10mIU/ml) was 99.29% in all children, and 86.48% children were reported with adequate anti-HBs titers (≥100mIU/ml).We found a significant higher proportions of early antenatal health care (< 13 gestational weeks), and term birth in children with adequate response compared with inadequate response (all P < 0.05). Logistic regression showed preterm birth was a negative factor for inadequate anti-HBs titers (ORadj = 1.868,95%CI 1.132-3.085,P = 0.015).ConclusionsChildren delivered by HBeAg positive mothers had higher risk of vertical transmission of HBV, despite completion of 3 doses of hepatitis B vaccine and HBIG injection. Inadequate anti-HBs level was significantly associated with preterm birth in HBsAg positive women.

A Novel Missense Mutation in the EDAR Gene and One Missense Mutation in EDA Gene in the Study of HED Patients in Iran

: Hypohidrotic ectodermal dysplasia (HED) is the most common type of ectodermal dysplasia that is the result of faulty ectodermal development leading to such ectodermal defects as hypotrichosis, anodontia or hypodontia, and hypohidrosis or anhidrosis. X-linked HED is caused by mutations in ectodysplasin A (EDA) gene and accounts for 90% of all HED cases. Autosomal HED is caused by mutations in other involved genes, such as EDA-receptor (EDAR) gene. In this study, we included two distinct families with three HED patients. We collected 5 mL of peripheral blood from the probands, associated parents, and 120 matched unrelated controls (from related ethnicity) without any ectodermal disorder. DNA was extracted using the routine salting-out protocol from blood leukocytes. Polymerase chain reaction (PCR) purification and bidirectional Sanger sequencing of the PCR products were performed. We identified p.R156H (c.467 G&gt;A) mutation in EDA gene in two affected brothers and their carrier mother (family 1) and a novel missense mutation c.1210G&gt;A (p.A404T) in EDAR gene in a 4-year-old affected boy and his heterogeneous parents (family 2). Clinical evaluation, genetic findings, and bioinformatic analysis supported deleterious effects of both identified mutations on the EDA and EDAR gene products, which should be considered in genetic assessment of HED cases in Southwest of Iran.

Community-Associated Methicillin-Resistant Staphylococcus Aureus Colonization in a Birth Cohort of Early Childhood: The Role of Maternal Carriage.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) colonization in infants may pose a risk for subsequent infection in children. The study aimed to determine S. aureus colonization patterns in infancy, and strain relatedness between maternal and infant colonization.Methods: A prospective cohort study was conducted for nasopharyngeal S. aureus detection in neonates at delivery; in children at 1, 6, 12, 24, 36, and 60 months of age; and from mothers immediately after the delivery of their baby and when their child is 1 month old. A questionnaire for infants and mothers was administered at each planned visit.Results: In total, 521 and 135 infant–mother dyads underwent nasopharyngeal swab collection at 1 month and immediately after delivery, respectively. Among the 521 dyads at 1 month of age, concordant S. aureus colonization was found in 95 dyads, including MRSA in 48.4% (46/95). No concordant MRSA carriage was present among the 135 dyads at delivery. The genetic relatedness of concurrent MRSA-colonized dyads showed that more than two-thirds (32/46 [69.6%]) had identical genotypes, mainly ST 59/PVL-negative/SCCmec IV. Infants aged 1 month had the highest incidence of S. aureus, and the trend declined to a nadir at the age of 12 months. Carrier mothers who smoked cigarettes may increase the risk of infant Staphylococcus colonization (odds ratio, 2.12; 95% confidence interval, 1.23–3.66; p < 0.01).Conclusions: Maternal–infant horizontal transmission may be the primary source of MRSA acquisition in early infancy. The avoidance of passive smoking could be recommended for the prevention of S. aureus carriage.

Molecular and clinical insights into complex genomic rearrangements related to MECP2 duplication syndrome

MECP2 duplication syndrome (MDS) is caused by copy number variation (CNV) spanning the MECP2 gene at Xq28 and is a major cause of intellectual disability (ID) in males. Herein, we describe two unrelated males harboring non-recurrent complex Xq28 rearrangements associated with MDS. Copy number gains were initially detected by quantitative real-time polymerase chain reaction and further delineated by high-resolution array comparative genomic hybridization, familial segregation, expression analysis and X-chromosome inactivation (XCI) evaluation in a carrier mother. SNVs within the rearrangements and/or fluorescent in situ hybridization (FISH) were used to assess the parental origin of the rearrangements. Patient 1 exhibited an intrachromosomal rearrangement, whose structure is consistent with a triplicated segment presumably embedded in an inverted orientation between two duplicated sequences (DUP-TRP/INV-DUP). The rearrangement was inherited from the carrier mother, who exhibits extreme XCI skewing and subtle psychiatric symptoms. Patient 2 presented a de novo (X;Y) unbalanced translocation resulting in duplication of Xq28 and deletion of Yp, originated in the paternal gametogenesis. Neurodevelopmental trajectory and non-neurological symptoms were consistent with previous reports, with the exception of cerebellar vermis hypoplasia in patient 2. Although both patients share the core MDS phenotype, patient 1 showed MECP2 transcript levels in blood similar to controls. Understanding the molecular mechanisms related to MDS is essential for designing targeted therapeutic strategies.

MECP2-Related Disorders in Males.

Methyl CpG binding protein 2 (MECP2) is located at Xq28 and is a multifunctional gene with ubiquitous expression. Loss-of-function mutations in MECP2 are associated with Rett syndrome (RTT), which is a well-characterized disorder that affects mainly females. In boys, however, mutations in MECP2 can generate a wide spectrum of clinical presentations that range from mild intellectual impairment to severe neonatal encephalopathy and premature death. Thus, males can be more difficult to classify and diagnose than classical RTT females. In addition, there are some variants of unknown significance in MECP2, which further complicate the diagnosis of these children. Conversely, the entire duplication of the MECP2 gene is related to MECP2 duplication syndrome (MDS). Unlike in RTT, in MDS, males are predominantly affected. Usually, the duplication is inherited from an apparently asymptomatic carrier mother. Both syndromes share some characteristics, but also differ in some aspects regarding the clinical picture and evolution. In the following review, we present a thorough description of the different types of MECP2 variants and alterations that can be found in males, and explore several genotype–phenotype correlations, although there is still a lot to understand.

540A simulation to evaluate HTLV-1 screening for pregnant women in prevention of adult T-cell leukemia

Abstract Background In Japan, the nation-wide screening program of pregnant women for HTLV-1 infection was launched in 2010 to prevent mother-to-child transmission. It is difficult to assess the effect of the screening program on adult T-cell leukemia (ATL) prevention by observational study because ATL develops after long-term (about 50 years) latency in HTLV-1 carriers. Thus, we assessed the effect of the screening using computer simulation. Methods We constructed our model that simulates lifetime history of the children born to HTLV-1 carrier mothers. Lifetime risks of ATL among the children in unscreened group and screened group were estimated employing Monte Carlo simulation. We developed three scenarios for the risk estimation of ATL in screened groups, each making different assumptions for the choice of feeding methods (formula feeding, short-term breast-feeding, and long-term breast-feeding). Results Our simulation revealed that lifetime risk of ATL among the children born to HTLV-1 carrier mothers was 1.19 % in unscreened group and 0.21 to 0.27 % in screened groups. Conclusions In Japan, it is estimated that there were 1,363 pregnant women with HTLV-1 infection in 2016 (Sekizawa 2018). From this figure, the estimated annual number of ATL patients prevented by the screening is 12.6 to 13.5. Key message HTLV-1 screening in pregnant women for one year is estimated to reduce the number of ATL among their children by about 13 in Japan.

Mother-to-Child Transmission of Human T-Cell Leukemia Virus Type 1: Mechanisms and Nutritional Strategies for Prevention.

Simple SummaryMother-to-child transmission (MTCT) of human T-cell leukemia virus type 1 (HTLV-1) is a major cause of adult T-cell leukemia (ATL). Owing to the poor prognosis of ATL and the fact that more than one million people have been infected with this virus, the HTLV-1 antibody screening test was established in Japan in 2010 for all pregnant women to detect carriers and prevent MTCT. Because breastfeeding is the most common route of postnatal MTCT, exclusive formula feeding is widely used as a measure to prevent MTCT. Recently, it was reported that there is no obvious difference in the efficacy of short-term breastfeeding for ≤3 months in preventing MTCT compared to that in exclusive formula feeding, and that a duration of breastfeeding that does not exceed four months can be effective for preventing MTCT.Approximately 95% of mother-to-child transmission (MTCT) of human T-cell leukemia virus type-1 (HTLV-1) is derived from prolonged breastfeeding, which is a major cause of adult T-cell leukemia (ATL). Exclusive formula feeding (ExFF) is therefore generally used to prevent MTCT. A recent cohort study revealed that 55% of pregnant carriers chose short-term breastfeeding for ≤3 months in Japan. Our meta-analysis showed that there was no significant increase in the risk of MTCT when breastfeeding was carried out for ≤3 months compared with ExFF (pooled relative risk (RR), 0.72; 95% confidence interval (CI), 0.30–1.77), but there was an almost threefold increase in risk when breastfeeding was carried out for up to 6 months (pooled RR, 2.91; 95% CI, 1.69–5.03). Thus, short-term breastfeeding for ≤3 months may be useful in preventing MTCT. Breastmilk is the best nutritional source for infants, and any approach to minimizing MTCT by avoiding or limiting breastfeeding must be balanced against the impact on the child’s health and mother–child bonding. To minimize the need for nutritional interventions, it is necessary to identify factors that predispose children born to carrier mothers to MTCT and thereby predict MTCT development with a high degree of accuracy.

Comparison of Carrier and de novo Pathogenic Variants in a Chinese DMD/BMD Cohort.

Background: Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessively inherited neuromuscular disorders caused by deletions, duplications, or small mutations in the DMD gene. With advances in prenatal diagnosis decreasing the number of affected offspring from carrier mothers, the frequency of de novo variants could increase. Therefore, determining the differences between the carrier and de novo variants of the DMD gene, which are rarely explored, is important for trial planning and genetic diagnosis in the future.Methods: A total of 440 patients, 349 of whom had DMD and 91 had BMD, diagnosed in our department between 2012 and 2019, along with their respective mothers, were included in this study. Multiplex ligation-dependent probe amplification was used to detected deletions and duplications in patients and their mothers. Small mutations were detected using next-generation sequencing in the patients, followed by Sanger sequencing in the mothers.Results: Deletions, duplications, and small mutations were identified in 204, 46, and 99 of the 349 patients with DMD and in 50, 10, and 31 of the 91 patients with BMD, respectively. De novo deletions were more concentrated in hotspot regions than carrier deletions of DMD/BMD. No clear bias was observed in the variant distribution between carriers, de novo duplications, and small mutations in DMD/BMD. The carrier frequency of DMD (61.6%) was lower than that of BMD (69.2%), but the difference was not statistically significant. The carrier frequency of deletions of the DMD gene (51.2%) was significantly lower than those of duplications (75%) and small mutations (81.5%).Conclusion: Compared to de novo deletions, deletions from carrier mothers had a wider distribution. Moreover, there was no significant difference between the carrier frequencies of DMD and BMD. Duplications and small mutations were more commonly inherited, while deletions were present de novo.

Group B streptococcus neonatal umbilical colonization managed by dry cord care in nurseries: A retrospective cohort study

Screening-based intrapartum antibiotic prophylaxis (IAP) has reduced the prevalence of early-onset group B Streptococcus (GBS) infection in newborns. Nevertheless, early-onset disease still occurs despite IAP, and IAP is not effective in preventing late-onset disease. This study aimed to determine the prevalence and risk factors of GBS neonatal umbilical colonization managed by dry cord care in Japan. Of 735 healthy newborns in the well-baby nursery at Saitama City Hospital, 353 from whom umbilical bacterial swabs were obtained before discharge were included in the analysis. Maternal and neonatal clinical characteristics were retrospectively reviewed. GBS was detected in 4.2% (15/353) of umbilical swabs; 13/15 (86.8%) were born to GBS-negative mothers. The median (IQR) age at umbilical swab collection was 4.0 (4.0-5.0) days. Comparison of clinical characteristics between GBS-positive and negative neonates revealed a significant difference in the proportion of vaginal deliveries (15/15 [100%] in GBS-positive neonates vs. 115/338 [34.0%] in GBS-negative neonates, p<0.0001). Of 15 GBS-positive neonates, 10 (66.7%) were also co-colonized with other enteric bacteria such as Escherichia coli. Vaginal delivery was a risk factor associated with GBS neonatal umbilical colonization in Japanese neonates. Co-colonization with multiple enteric bacterial species implicates vertical transmission of GBS from undetected carrier mothers during passage through the birth canal.