Asymptomatic Mother Research Articles

Evaluation of Liver Function Tests in Normal Pregnancy-An Observational Epidemiological Study-Kumbakonam Urban Rural Epidemiological Study-KURES 10

Early interpretation of liver function tests (LFTs) can result in timely management and it may decrease the incidence of complications in both the mother and the foetus. Normal LFTs don't always imply a normal liver. A number of drawbacks can occur when interpreting basic blood LFTs. Abnormal Liver Function Tests (LFTs) in pregnancy must be properly interpreted to avoid diagnostic pitfalls. we did a routine testing in 498 asymptomatic antenatal mothers in the third trimester. Ninety-seven percentage of mothers had normal bilirubin while 93 % had normal enzyme levels. The other abnormal values were also within 1 to 1.5 % above the normal. No mother had any symptoms. Only two patients had gallstones whose LFTs were normal. Two mothers had tattoo marks while the other two were HbSAg positive. All the 498 mothers had an uneventful progress towards delivery. Cross consultation done on a few cases with abnormal values were non-contributory. Pregnancy-related disorders are the most common reason for unusual liver function tests during pregnancy, especially in the third trimester. We omitted such cases to support our hypotheses of avoiding undue testing. The most prevalent is pre-eclampsia-related disorder. This is the first such study on a huge sample size. We suggest a routine testing of LFTs is not needed in otherwise healthy antenatal mothers.

Neonatal Lupus Erythematosus with Congenital Complete Heart Block in an Asymptomatic Mother

Neonatal Lupus Erythematosus with Congenital Complete Heart Block in an Asymptomatic Mother

Histopathological changes in the placentas of mothers with a history of coronavirus disease 2019 infection in pregnancy- A comparative cross-sectional study

This study aimed to evaluate histopathological changes in the placentas of mothers who had contracted COVID-19 during pregnancy. This prospective study involved the histopathological assessment of two groups of placentas submitted for evaluation to the Department of Histopathology at Khoula Hospital, Oman. The first group consisted of 48 placentas derived from COVID-19-positive pregnant women delivered at the centre between March 2020 and March 2021. The control group consisted of an additional 48 placentas derived from asymptomatic mothers who were not tested for COVID-19 but were assumed to be negative. All placentas underwent gross and microscopic histopathologic examination. Placental lesions were classified according to the Amsterdam system. There was a significantly higher frequency of fibrin thrombi at the terminal villi in placentas derived from the COVID-19-positive group compared to the control group (72.9% versus 0%; p-value = 0.001). Also, villous hypoperfusion was significantly more common in COVID-19-positive placentas than in controls (16.7% versus 0%; p-value = 0.006). However, no significant differences between the two groups were noted with regards to the frequency of other histopathologic features, including decidual vasculopathy, chorioamnionitis, funisitis, intervillositis, perivillous fibrin deposition, and infarction.

Identification of a novel CACNA1F mutation in a Chinese family with CORDX3.

X-linked cone-rod dystrophy (CORDX) is one form of inherited retinal disorders (IRDs) characterized by progressive dysfunction of photoreceptor. Three types of CORDX were reported and CACNA1F gene defect can cause CORDX3. The aim of this study was to investigate the pathogenic variant in a Chinese family with IRD. The two affected subjects including the proband and his elder sister underwent ophthalmic examinations. Whole exome sequencing (WES) was performed in the proband at first, then co-segregation analysis was performed in the family by Sanger sequencing. Minigene approach was used to verify the effect of the mutation on the splicing of CACNA1F. X-chromosomal inactivation assay was performed to evaluate the inactivation patterns of the female carriers. The ophthalmic examination results of the proband fit the clinical description of CORDX3, and the female patient presented with only mild symptoms due to mildly skewed X-chromosomal inactivation (ratio 67: 33). Molecular genetic testing identified a novel splice-site mutation c.3847-2A > G in CACNA1F (NM_005183.4) gene in the patients, which inherited from their asymptomatic mother. Minigene approach confirmed that c.3847-2A > G could affect the splicing of CACNA1F. Our study identified a novel splice-site mutation in the CACNA1F gene, which expanded the mutational spectrum of CACNA1F-releated diseases and demonstrated the importance of combining clinical and genetic testing in the diagnosis of IRDs.

Members of the Fusarium oxysporum Complex Causing Wilt Symptoms inMedical Cannabis in Israel, Italy, and North America Comprise a Polyphyletic Assemblage.

Members of the Fusarium oxysporum complex are ubiquitous soilborne fungal pathogens causing wilt diseases in various plant hosts. Fusarium oxysporum (Fo) f. sp. cannabis was first reported causing wilt disease in hemp in Italy in 1962. To date, Fusarium wilt continues to cause concern in industrial and medicinal cannabis cultivation worldwide. During a 3-year period (2018 to 2021), Fo strains were isolated from medical cannabis plants (Cannabis sativa) exhibiting wilt symptoms that were cultivated in numerous commercial farms in Israel. A diverse set of these strains was subjected to molecular phylogenetic analyses to assess their genetic diversity and to compare them with other f. sp. cannabis isolates included in prior studies. Maximum likelihood bootstrap analysis of a partial translation elongation factor (TEF1) dataset, which included 24 f. sp. cannabis sequences, revealed that the 11 strains from Israel comprised five TEF1 haplotypes. Two of the haplotypes from Israel were identical to isolates previously reported from British Columbia and California and British Columbia and Ontario. Overall, the 24 f. sp. cannabis sequences included 12 unique TEF1 haplotypes. These were phylogenetically diverse, suggesting that pathogenicity to C. sativa may have evolved independently within the F. oxysporum complex. Pathogenicity tests of the Israeli strains were confirmed by Koch's postulates assays. Strains of the five different f. sp. cannabis TEF1 haplotypes all caused wilt in cannabis seedlings but with varying levels of aggressiveness. The same isolates that originated from asymptomatic infected mother plants were found in wilted cuttings indicating that the pathogen can be spread via propagation material.

Prenatal Phenotypical Discrepancy in Monozygotic Twins with Tuberous Sclerosis Complex

Abstract Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder characterized by the development of hamartomas in the brain, heart, skin, kidney, lung, retina, and so on. One fetus from family 1 had a cardiac rhabdomyoma from 21 weeks and 6 days of gestational age, and developed multiple rhabdomyomas and tubers in the brain at 23 weeks and 5 days. The counter monozygotic twin fetus remained negative throughout the pregnancy according to imaging examination. A nonsense mutation in TSC2 (c.4762C>T, p.Gln1588*) was identified in both twins, but not in the mother. Family 2 was one pair of twin fetuses caused by a microdeletion of exon 30 within TSC2 inherited from their apparently asymptomatic mother with mosaic status. The larger fetus was identified as having the first cardiac rhabdomyoma from 17 weeks and 4 days of gestational age. The smaller fetus developed multiple rhabdomyomas until 25 weeks and 6 days of gestational age. Both families terminated the pregnancy. Here, we provide intrauterine examples of clinical variability among monozygotic twins suffering from TSC.

X‑linked adrenoleukodystrophy caused by maternal ABCD1 mutation and paternal X chromosome inactivation

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It is caused by defects in the ATP-binding cassette subfamily D member 1 (ABCD1) gene, resulting in impaired peroxisomal β-oxidation of very-long-chain fatty acids (VLCFAs). As an X-linked recessive disease, female X-ALD carriers are typically asymptomatic. In the present study, a 7-year-old girl was diagnosed with cerebral ALD. Brain magnetic resonance imaging revealed asymmetric demyelination of bilateral white matter. Plasma VLCFAs level showed a substantial increase. Whole exome and Sanger sequencing revealed an ABCD1 c.919C>T (p.Q307X) heterozygous pathogenic mutation, which was inherited from the asymptomatic mother. X chromosome inactivation (XCI) analysis revealed that the normal paternal X chromosome was almost completely inactivated. Thus, the maternal ABCD1 mutation and paternal XCI were responsible for causing the disease in the patient. XCI may be one reason female X-ALD carriers can be symptomatic.

Contribution of DNA methylation profiling to the reclassification of a variant of uncertain significance in the KDM5C gene

KDM5C encodes a demethylase of the histone H3 lysine 4 residue, involved in chromatin regulation and gene expression. Hemizygous KDM5C pathogenic variants cause X-linked intellectual disability of Claes-Jensen type. Because of its mode of inheritance and the low specificity of the clinical phenotype, interpretation of variants can be difficult, hence the need for functional studies and biomarkers specific to this disorder. We present the case of a male patient with intellectual disability, behavioral abnormalities and subtle dysmorphic features, in which genetic investigation identified a hemizygous novel missense KDM5C variant of uncertain significance (VUS), inherited from his asymptomatic mother and present in his paucisymptomatic sister. We assessed the global genomic DNA methylation status from a whole blood sample of the proband. Global DNA methylation profiling specifically identified the recently discovered epi-signature of Claes-Jensen syndrome. This result served as a biomarker which independently highlighted KDM5C as the cause of the disorder in this patient. Because of the X-linked mode of inheritance, variant reclassification had a high impact on genetic counseling in this family. This example highlights the value of global methylome profiling in situations of variants of uncertain significance in genes with a known specific epi-signature.

Clinical and immunological assessment of APDS2 with features of the SHORT syndrome related to a novel mutation in PIK3R1 with reduced penetrance.

Monoallelic loss-of-function (LOF) mutations in the phosphatidylinositol 3-kinase (PIK3R1) gene affecting the inter-Src homology 2 domain of the p85α regulatory subunit of phosphoinositide--3-kinase δ (PI3Kδ) cause the activated PI3K δ syndrome (APDS2). APDS2 is defined as a primary antibody deficiency, developmental abnormalities within the B and T lymph cell compartments, and immune dysregulation. The genetic defect of APDS2 is shared with that of the SHORT syndrome, characterized by short stature, joint hyperextensibility, ocular depression, Rieger anomaly, and delayed tooth eruption. LOF variants in an intronic splice site (c.1425+1G.C/A/T) in the PI3KR1 gene have been identified in patients affected with both APDS2 and SHORT syndrome. Herein, we report a novel c.1644-1648del (p.Asp548Glufs*6) variant in a pediatric patient with the APDS2-related immunodeficiency, who presents with mild phenotypic features of the SHORT syndrome, congenital chest wall deformity, and IgE-mediated food allergy. The same variant was also identified in the patient's hitherto asymptomatic mother, implicating an incomplete penetrance. Regular monitoring by a multidisciplinary team under the pediatric clinical immunologist's supervision to implement appropriate diagnostic procedures and treatment modalities is of paramount importance. Further studies are required to better define the genotype-phenotype correlation in patients with the PIK3R1 gene mutations and to better delineate the mutual relationship between APDS2 and the SHORT syndrome.

Computational analysis of missense filamin-A variants, including the novel p.Arg484Gln variant of two brothers with periventricular nodular heterotopia.

Periventricular nodular heterotopia (PNH) is a cell migration disorder associated with mutations in Filamin-A (FLNA) gene on chromosome X. Majority of the individuals with PNH-associated FLNA mutations are female whereas liveborn males with FLNA mutations are very rare. Fetal viability of the males seems to depend on the severity of the variant. Splicing or severe truncations presumed loss of function of the protein product, lead to male lethality and only partial-loss-of-function variants are reported in surviving males. Those variants mostly manifest milder clinical phenotypes in females and thus avoid detection of the disease in females. We describe a novel p.Arg484Gln variant in the FLNA gene by performing whole exome analysis on the index case, his one affected brother and his healthy non-consanguineous parents. The transmission of PNH from a clinically asymptomatic mother to two sons is reported in a fully penetrant classical X-linked dominant mode. The variant was verified via Sanger sequencing. Additionally, we investigated the impact of missense mutations reported in affected males on the FLNa protein structure, dynamics and interactions by performing molecular dynamics (MD) simulations to examine the disease etiology and possible compensative mechanisms allowing survival of the males. We observed that p.Arg484Gln disrupts the FLNa by altering its structural and dynamical properties including the flexibility of certain regions, interactions within the protein, and conformational landscape of FLNa. However, these impacts existed for only a part the MD trajectories and highly similar patterns observed in the other 12 mutations reported in the liveborn males validated this mechanism. It is concluded that the variants seen in the liveborn males result in transient pathogenic effects, rather than persistent impairments. By this way, the protein could retain its function occasionally and results in the survival of the males besides causing the disease.

Obstetric analgesia and anaesthesia in SARS-CoV-2-positive parturients across 10 maternity units in the north-west of England: a retrospective cohort study.

SummarySince the start of the COVID‐19 pandemic, few studies have reported anaesthetic outcomes in parturients with SARS‐CoV‐2 infection. We reviewed the labour analgesic and anaesthetic interventions utilised in symptomatic and asymptomatic parturients who had a confirmed positive test for SARS‐CoV‐2 across 10 hospitals in the north‐west of England between 1 April 2020 and 31 May 2021. Primary outcomes analysed included the analgesic/anaesthetic technique utilised for labour and caesarean birth. Secondary outcomes included a comparison of maternal characteristics, caesarean birth rate, maternal critical care admission rate along with adverse composite neonatal outcomes. A positive SARS‐CoV‐2 test was recorded in 836 parturients with 263 (31.4%) reported to have symptoms of COVID‐19. Neuraxial labour analgesia was utilised in 104 (20.4%) of the 509 parturients who went on to have a vaginal birth. No differences in epidural analgesia rates were observed between symptomatic and asymptomatic parturients (OR 1.03, 95%CI 0.64–1.67; p = 0.90). The neuraxial anaesthesia rate in 310 parturients who underwent caesarean delivery was 94.2% (95%CI 90.6–96.0%). The rates of general anaesthesia were similar in symptomatic and asymptomatic parturients (6% vs. 5.7%; p = 0.52). Symptomatic parturients were more likely to be multiparous (OR 1.64, 95%CI 1.19–2.22; p = 0.002); of Asian ethnicity (OR 1.54, 1.04–2.28; p = 0.03); to deliver prematurely (OR 2.16, 95%CI 1.47–3.19; p = 0.001); have a higher caesarean birth rate (44.5% vs. 33.7%; OR 1.57, 95%CI 1.16–2.12; p = 0.008); and a higher critical care utilisation rate both pre‐ (8% vs. 0%, p = 0.001) and post‐delivery (11% vs. 3.5%; OR 3.43, 95%CI 1.83–6.52; p = 0.001). Eight neonates tested positive for SARS‐CoV‐2 while no differences in adverse composite neonatal outcomes were observed between those born to symptomatic and asymptomatic mothers (25.8% vs. 23.8%; OR 1.11, 95%CI 0.78–1.57; p = 0.55). In women with COVID‐19, non‐neuraxial analgesic regimens were commonly utilised for labour while neuraxial anaesthesia was employed for the majority of caesarean births. Symptomatic women with COVID‐19 are at increased risk of significant maternal morbidity including preterm birth, caesarean birth and peripartum critical care admission.

A Nonsense Variant of ZNF462 Gene Associated With Weiss-Kruszka Syndrome-Like Manifestations: A Case Study and Literature Review.

Objective: This study aims to explore the clinical characteristics and genetic basis of a patient with unilateral ptosis and unilateral hearing impairment in pedigree analysis. Methods: The clinical data of the child and his father were collected. The genomic DNA of the patient and his relatives were extracted from their peripheral blood samples and subjected to trio-whole-exome sequencing (trio-WES) and copy number variation analysis. Sanger sequencing was used to verify the potential variant. Results: The sequencing analysis identified a heterozygous nonsense variant c.6431C > A (p.Ser2144*) in the ZNF462 gene (NM_021224.6) in the child and his father, whereas the locus in his asymptomatic mother, brother, and grandparents was found to be the wild type, which is an autosomal dominant inheritance. The new genetic variant has not been previously reported in the ClinVar and HGMD databases and the Genome Aggregation Database (gnomAD). Conclusion: This is the first incidence of Weiss–Kruszka syndrome relating to the nonsense variant in the ZNF462 gene in China. The finding from this study is novel in its expansion of the variant spectrum of the ZNF462 gene and clarifies the genetic etiology of the patient and his father.

Neonatal lupus : 5 pediatric cases

Neonatal lupus erythematosus is a rare condition that manifests itself in different types of damage, whether cutaneous, hepatic, hematological, neurological or even cardiac. We report here three cases of neonatal lupus occurring in newborns, two of them from completely asymptomatic mothers and revealed by cardiac involvement and one case revealed by skin involvement.

Novel insights into PORCN mutations, associated phenotypes and pathophysiological aspects

BackgroundGoltz syndrome (GS) is a X-linked disorder defined by defects of mesodermal- and ectodermal-derived structures and caused by PORCN mutations. Features include striated skin-pigmentation, ocular and skeletal malformations and supernumerary or hypoplastic nipples. Generally, GS is associated with in utero lethality in males and most of the reported male patients show mosaicism (only three non-mosaic surviving males have been described so far). Also, precise descriptions of neurological deficits in GS are rare and less severe phenotypes might not only be caused by mosaicism but also by less pathogenic mutations suggesting the need of a molecular genetics and functional work-up of these rare variants.ResultsWe report two cases: one girl suffering from typical skin and skeletal abnormalities, developmental delay, microcephaly, thin corpus callosum, periventricular gliosis and drug-resistant epilepsy caused by a PORCN nonsense-mutation (c.283C > T, p.Arg95Ter). Presence of these combined neurological features indicates that CNS-vulnerability might be a guiding symptom in the diagnosis of GS patients. The other patient is a boy with a supernumerary nipple and skeletal anomalies but also, developmental delay, microcephaly, cerebral atrophy with delayed myelination and drug-resistant epilepsy as predominant features. Skin abnormalities were not observed. Genotyping revealed a novel PORCN missense-mutation (c.847G > C, p.Asp283His) absent in the Genome Aggregation Database (gnomAD) but also identified in his asymptomatic mother. Given that non-random X-chromosome inactivation was excluded in the mother, fibroblasts of the index had been analyzed for PORCN protein-abundance and -distribution, vulnerability against additional ER-stress burden as well as for protein secretion revealing changes.ConclusionsOur combined findings may suggest incomplete penetrance for the p.Asp283His variant and provide novel insights into the molecular etiology of GS by adding impaired ER-function and altered protein secretion to the list of pathophysiological processes resulting in the clinical manifestation of GS.

The Need for Mandatory COVID-19 Testing among Pregnant Women: Lessons from Routine Testing

The coronavirus disease 2019 (COVID-19) continues to ravage the globe, significantly affecting vulnerable groups like people with chronic illnesses and pregnant women. Unlike early in the pandemic, recent evidence indicates that COVID-19 causes various complications in pregnancy like preterm birth and preeclampsia. However, it is unclear how COVID-19 precisely interplays with pregnancy, and which trimester the infection is most detrimental is variable. Some pregnancy-related complications, such as preeclampsia and eclampsia, share similar pathophysiological mechanisms and clinical features to COVID-19; as a result, they present a diagnostic challenge, with one condition being mistaken for the other, leading to poor pregnancy outcomes. We discovered COVID-19 among asymptomatic mothers who later developed complications and those who initially presented with complications based on our experiences performing routine COVID-19 tests, which were published in various case reports. These patients were mostly in their third trimester, and we believe the outcomes would have been worse if COVID-19 had not been detected early and treated promptly. Therefore, this clinical opinion is structured to show how COVID-19 affects pregnancy and which trimester the infection is most detrimental based on the available data to support routine testing of COVID-19 among pregnant women and to maximize benefits while minimizing costs.

Inaugural Seizures Revealing COVID-19 in an Immunocompetent Infant at the University Teaching Hospital (UTH) of Bouaké

Introduction: Children are likely to present with atypical and non-specific clinical manifestations of COVID-19, unlike adults. The aim of this observation is to identify the difficulties related to the diagnosis and the curative and preventive management of SARS-CoV-2 infection in children. Observation: This is a 15-month-old infant admitted for febrile seizures. The interrogation revealed signs evolving 48 hours before his admission marked by post-prandial vomiting, wet cough, hypotonia, food refusal, incessant crying, fever, and seizures. His antecedents can be summed up as an uneventful pre- and per-natal period, good eating habits, good psychomotor and staturo-ponderal development, and outdated vaccination. The physical and paraclinical examination made it possible to retain the diagnosis of severe pneumonia. The initial management consisted of oxygenation, hydroelectrolyte intake, antibiotic therapy, and neurosedation. The evolution 3 days later was marked by a worsening of the clinical features, and the hypothesis of infection with SARS-CoV-2 was raised. The nasopharyngeal swab for COVID-19 RT-PCR performed was positive. The infant was isolated in the intensive care unit, where he received oxygen therapy with a mask, enteral nutrition, antibiotic therapy, corticosteroid therapy, and adequate nursing. The evolution was favorable 48 hours later. In addition, his asymptomatic mother and 14-year-old brother were placed in isolation after a positive RT-PCR COVID-19 test. Her father who was very often away from home for professional reasons was negative for COVID-19 RT-PCR. They all four live in the same 3-room house. Conclusion: Childhood COVID-19 has many facets. Clinicians should think about it in the face of any infectious manifestation, in order to avoid delays in treatment and improve the prognosis.

The management of newborns of mothers who are COVID-19 positive in a "COVID-free" hospital in Italy

The strategies planned by the Italian Ministry of Health to manage the COVID-19 pandemic include the centralisation of positive subjects in specific centres (Hubs) as well keeping others "COVID free". However due to the large number of positive subjects, the beds available have sometimes been inadequate. All pregnant women, at admission to the hospital, are screened and, if positive, sent to an Hub, but in the case of known positivity after birth, without bed availability, we structured a plan to complete the hospitalisation in our department of asymptomatic mothers with negative newborns. From October to December 2020, eleven babies were born to mothers who tested COVID-19-positive after delivery. Seven of them completed hospitalisation in our department. No complications in mother-baby dyads and no contagion among hospital staff were found. This strategy, even in a limited number of cases, allowed the management without complications for both patients and healthcare professionals.

Placental Pathology in Maternal Ornithine Transcarbamylase Deficiency.

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder, inherited in an X-linked manner. Males are severely affected. Female phenotypes vary from asymptomatic to severe, and symptoms may be triggered by high metabolic states like childbirth. Literature on OTC deficiency in pregnancy and placental pathology is limited. Pathology records were searched at a single referral center from 2000-2020 and identified three placental cases from two mothers heterozygous for OTC deficiency. Placental pathology and maternal and neonatal history were reviewed in detail. The placenta from one symptomatic mother carrying an affected male fetus showed widespread high-grade fetal vascular malperfusion (FVM) lesions of varying age. These lesions were not seen in the two placentas from the asymptomatic mother. In cases of symptomatic maternal OTC deficiency, our findings highlight the need for placental examination. Since thrombotic events in the placenta have the potential to associate with fetal and neonatal endothelial damage, a high index of suspicion for neonatal thrombosis may be warranted.

Identification of of a PAX2 mutation from maternal mosaicism causes recurrent renal disorder in siblings

BackgroundPAX2-related disorder is an autosomal dominant disorder characterized by renal and eye abnormalities. Some patients may present with isolated renal abnormalities without obvious ocular abnormalities. It is associated with mutations in paired box gene 2 (PAX2), which is one of the families of paired box transcription factor genes. Studies on mosaicism have been limited in PAX2-related disorder, as only three families with mosaic PAX2 mutations have been reported in the literature. MethodsThe proband with multicystic dysplastic kidneys from a Chinese family was recruited in our study. Detailed clinical symptoms were enquired. Trio-based whole exome sequencing (WES), SNP array, sanger sequencing and droplet digital PCR (ddPCR) were used to characterize etiology in the proband. Prenatal diagnosis was performed through amniocentesis and prenatal ultrasound when the proband's mother was further pregnant at 20 weeks. ResultsA heterozygous missense mutation in PAX2 (c.194 T > C) was identified in the proband. His asymptomatic mother has the same mutation with somatic mosaicism ratio of 22%. The mutation was also detected in the fetus. Prenatal ultrasound showed that bilateral hyperechogenic kidneys with decrease of renal size. ConclusionsThis is the first report on PAX2 mosaicism in a Chinese family. Identifying PAX2 mosaicism provides more evidence for estimating recurrence risk. Our findings have important implications on genetic counseling for patients with PAX2-related disorder and provide an effective diagnostic technology for mosaicism.

Clinical phenotype and genetic analysis of MECP2 duplication syndrome

To analyze the clinical symptom and parental origin of patients with MECP2 duplication syndrome in order to provide a basis for genetic counseling and prenatal diagnosis. Clinical symptoms of four patients who were diagnosed with MECP2 duplication syndrome by copy number variation sequencing (CNV-Seq) were reviewed. The maternal origin of the duplications were verified. All patients were males, and CNV-Seq revealed that they have all harbored a duplication in the Xq28 region spanning 0.32 ~ 0.86 Mb, which were derived from asymptomatic mothers. The clinical symptoms of three patients with three copies included delayed speech, intellectual disability, and muscular hypotonia, while the patient with four copies had died at 6 months after birth, with clinical symptoms including recurrent infections, seizures, and spasticity. The four cases of MECP2 duplication syndrome have shown complete penetrance and have all derived from asymptomatic mothers. As a stable and reliable method, CNV-Seq can accurately detect the MECP2 duplication syndrome.