ABSTRACT
Objective:To evaluate the value of monitoring regional cerebral oxygen saturation (rSO 2) in the prognosis of comatose children in pediatric intensive care unit (PICU). Methods:A total of 127 coma children who admitted to PICU at Henan Children′s Hospital from January 2019 to September 2021 were collected and divided into mild[Glasgow coma score(GCS): 13-15], moderate(GCS: 9-12) and severe coma(GCS: 3-8) groups according to GCS.A cerebral oxygen monitor was used to monitor the rSO 2 of all children before treatment, and on the 3rd, 7th and 14th day after treatment.The outcomes were assessed according to the pediatric cerebral performance category (PCPC), and the children were divided into recovery group(PCPC score: 1), disability group(PCPC score: 2-4) and poor prognosis group(PCPC score: 5-6). Multiple linear regression and receiver operating characteristic(ROC) curve were used to analyze the correlation between rSO 2 and PCPC score. Results:rSO 2 in mild, moderate and severe coma groups before treatment were (78.06±3.21)%, (66.07±6.05)%, and (52.87±6.49)%, respectively ( F=209.263, P<0.05). rSO 2 before treatment was positively correlated with GCS( r=0.806, P<0.05). There were significant differences in rSO 2 among recovery group, disability group and poor prognosis group before treatment and that on the 3rd, 7th and 14th day after treatment ( P<0.05). Notably, rSO 2 in recovery group was higher than that in disability group, and rSO 2 in disability group was higher than that in poor prognosis group.The rSO 2 of three groups showed an increasing trend over time ( P<0.05). Multiple linear regression analysis showed that rSO 2 on the 7th and 14th day of treatment were independent prognostic factors ( OR -0.042, 95% CI -0.082~0.003, P<0.05; OR -0.047, 95% CI -0.094~0.000, P<0.05). ROC analysis showed that rSO 2 on the 7th day of treatment had a relatively higher prognostic value for children in coma, and the area under the ROC curve for predicting the prognosis of abnormal brain function and no wakefulness were 0.741 and 0.746, respectively. Conclusion:Monitoring rSO 2 has predictive value for the prognosis of brain function of coma children in PICU, in which the prognostic value of rSO 2 on the 7th day after treatment is relatively higher and can be used as a reference index for prognosis assessment of coma children in PICU.
ABSTRACT
Objective:To explore the value of immediate bedside blood culture in the adjustment of antibiotics for children with bloodstream infections in pediatric intensive care units(PICU).Methods:Retrospective analysis of children in PICU at Henan Children′s Hospital from May 2017 to March 2021 was conducted.The cases were divided into laboratory blood culture(LBC) group and satellite blood culture(SBC) group according to different blood culture methods.The difference in the time to blood culture incubation, time to blood culture positivity, microbial results time and antibiotic adjustment time were compared between two groups.Results:A total of 3 720 blood cultures were completed in 2 718 children, including 1 888 in LBC group and 1 832 in SBC group, with a positive rate of 3.5% in LBC group and 4.9% in SBC group, and a significantly higher positive rate in SBC group compared to LBC group( χ2=3.954, P=0.046). The differences in age, sex, site of infection, survival rate at 28 d after discharge, pediatric critical illness score, and pediatric risk of mortality Ⅲ score between LBC group and SBC group with positive blood cultures were not statistically significant ( P>0.05). Children in SBC group had significantly shorter specimen receipt time, time to obtain microbiological results, and antibiotic adjustment time than those in LBC group[0.33(0.03, 1.78) h vs. 3.38(1.38, 7.29) h, (57.40±21.92) h vs. (68.14±21.26) h, and (52.53±27.23) h vs. (66.41±28.57) h, all P<0.05]. Conclusion:Immediate bedside blood culture shortens the time from culture to final result reporting, increases the positive rate of blood culture, and saves time on accurate antibiotic treatment for critically ill children.
ABSTRACT
Objective:To summarize the clinical phenotype and genetic characteristics of Poirier-Bienvenu neurodevelopmental syndrome associated with CSNK2B gene variation. Methods:The clinical and genetic data of a child with Poirier-Bienvenu neurodevelopmental syndrome caused by shear variant of CSNK2B gene who was diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University in March 2022 were collected. Previous relevant literature at home and abroad was reviewed to summarize the clinical characteristics of the disease. Results:The child was a girl aged 13 months, mainly due to "intermittent convulsions for 2 months" for consultation. The clinical manifestations of the girl were normal face, generalized tonic-clonic seizures, low intelligence, language and motor retardation, and there was no abnormality in the long-range video electroencephalography and the head magnetic resonance imaging. No abnormality was found in chromosome karyotype analysis and chromosome coefficient of copy variation analysis. The whole exon gene sequencing test indicated that the child carried de novo heterozygous shear variant of CSNK2B gene c.291+5G>C, which had not been reported in the literature. According to the clinical manifestations and genetic examination results of the child, the diagnosis of Poirier-Bienvenu neurodevelopmental syndrome was clear. The CSNK2B gene of the proband′s parents and the twin sister was wild-type. The application of sodium valproate anti-seizure medication could effectively control the seizures of the child, and by giving rehabilitation function training, the child′s language and gross motor function was improved. Conclusions:The Poirier-Bienvenu neurodevelopmental syndrome is a rare autosomal dominant disorder caused by variants in the CSNK2B gene. The clinical manifestations are infancy-onset seizures, intellectual development disorders, language and motor development disorders, etc, and the video electroencephalogram and skull magnetic resonance are mostly normal. The CSNK2B gene shear variant is the genetic etiology of the proband.
ABSTRACT
Objective:To analyze the clinical characteristics and genetic variation of 2 children with developmental and epileptic encephalopathy 8 (DEE8).Methods:Whole-exome sequencing (WES) was performed to determine the potential variants in the probands. Candidate variants identified by WES were validated by Sanger sequencing and quantitative real-time polymerase chain reaction. X chromosome inactivation (XCI) detection was performed in the proband 1′s mother and proband 2 to detect the allelic expression difference of ARHGEF9. Results:Both of the cases showed global developmental delay. Proband 1 presented with delayed motor and speech development, intellectual disability, and seizures. Electroencephalography of proband 1 showed slow background activity, with spikes, spike and waves in bilateral frontal and midline regions during sleep. While proband 2 showed delay in acquisition of language, motor skills, and cognition, but no seizures. It was identified that proband 1 carried a novel maternally derived heterozygous splicing variant (c.925-2A>T) in ARHGEF9 by WES, which was verified in Sanger sequencing. The XCI in proband 1′s mother was observed, and the expression ratio of mutant ARHGEF9 and wild-type was 0∶100%. A novel exon 3-10 heterozygous deletion of ARHGEF9 was identified in proband 2, and this variant was not found in his unaffected parents. Conclusions:DEE8 disorders are relatively rare. Most of the patients have varying degrees of neurodevelopmental phenotype, but epilepsy is not a specific clinical manifestation. ARHGEF9 gene deletion and splicing variation may be the genetic cause of the 2 probands, and above findings have enriched the spectrum of variation and phenotype of DEE8.
ABSTRACT
Objective:To summarize the clinical phenotype and CUX2 gene variation characteristics of developmental epileptic encephalopathy type 67 confirmed by whole exome sequencing. Methods:Clinical data of 1 case diagnosed as CUX2 gene mutations related developmental epileptic encephalopathy type 67 in the Children′s Hospital Affiliated to Zhengzhou University in January 2021 were collected, the patient′s clinical characteristics, genetic testing, head imaging, electroencephalogram results and treatment were summarized, and the patient was regularly followed-up every 3 months. At the same time, the domestic and foreign literatures on epileptic encephalopathy caused by CUX2 gene mutation were reviewed. Results:The proband was a 6 years and 4 months old girl. The main clinical manifestations included focal origin progression to bilateral tonic-clonic seizures, retardation of intellectual, language, and motor development, autistic behavior, hyperactivity disorder, and involuntary hand clapping. The video electroencephalogram showed extensive spiny slow wave and multi-spiny slow wave emission in waking and sleeping stages, and spiny slow wave and spiky slow wave emission in bilateral anterior head in sleeping stage. Brain magnetic resonance imaging (MRI) plain scan and T 2-fluid attenuated inversion recovery (T 2-FLAIR) thin layer scan showed that the signal of the left hippocampus was higher than that of the right, and the left hippocampus was slightly swollen. One month later, the brain MRI and T 2-FLAIR were reexamined. The left hippocampal signal was still slightly higher and decreased, and the hippocampal volume was slightly reduced. Whole exome sequencing showed the CUX2 gene with c.1768G>A(p.Glu590Lys) heterozygous missense variant, which was a reported de novo pathogenic variant and both of her parents were wild-type. A total of 10 cases of new heterozygous missense variants in CUX2 gene [c.1768G>A (p.Gelu590Lys)] were reported in 4 literatures. No relevant cases have been reported in China. Conclusions:Developmental epileptic encephalopathy type 67 is relatively rare. The main clinical features are seizures, global developmental delay, movement disorders, athetosis, autism and hyperactivity disorder. The heterozygous missense variant c.1768G>A (Glu590Lys) of CUX2 gene maybe the genetic cause of this case.
ABSTRACT
Clinical data and genetic mutation characteristics of a patient with Coffin-Siris syndrome by 6q25.3 deletion were summarized. The child was a 7-year and 6-month old girl who had feeding difficulties, repeated infection, language and motor retardation, low intelligence, laryngeal cartilage dysplasia, thick eyebrows, sparse teeth, hairy back, hyperactivity and aggressive behavior, seizures and ataxia. There was no abnormality in chromosomal karyotype analysis by proband; genomic copy number variant sequencing (CNV-seq) indicated approximately 4.27 Mb heterozygous deletion in chromosome 6q25.3 region, with 17 genes including ARID1B gene, father maternal CNV-seq showing no abnormalities. Trio-whole-exome sequencing showed the proband missed all exons 1-20 of the ARID1B gene, with wild-type parents. The proband had severe clinical symptoms and haplodose insufficiency which was the genetic etiology.
ABSTRACT
OBJECTIVE@#To conduct clinical and genetic analysis of two male patients with atypical Rett syndrome.@*METHODS@#Collection of clinical data in the two patients and these parents; whole exome sequencing (WES) was used to detect the potential variants, which were verified by Sanger sequencing. X chromosome inactivation (XCI) detection is performed in the Patient 1's mother to detect the allelic expression difference of the MECP2 gene.@*RESULTS@#Patient 1, a 5-year and 10-month-old boy, had mental disorders and mild intellectual disability (ID) (IQ: 54), whose mother had ID. Patient 2 was a 9-month and 18-day-old male presented with recurrent infections, respiratory insufficiency, hypotonia and global developmental delay. WES indentified a hemizygous mutation, c.499C>T (p.R167W), in the MECP2 gene in patient 1, which was inherited from his mother. The inactivation of X chromosome is skewed, and the expression ratio of wild-type and mutant MECP2 is 100%:0. Patient 2 was found a de novo splicing mutation, c.62+2_62+3del in the MECP2 gene. They were both reported pathogenic variant related to Rett syndrome. c.499C>T (p.R167W) was defined as likely pathogenic (PS1+PM2+PP3) and c.62+2_62+3del was pathogenic (PVS1+PM2+PM6) based on American College of Medical Genetics and Genomics standards and guidelines.@*CONCLUSION@#Both the two patients were diagnosed with rare male Rett syndrome, which had atypical clinical manifestations and large difference. Above foundings have revealed novel phenotypes in Chinese male patients with Rett syndrome.
Subject(s)
Female , Humans , Male , Craniosynostoses , Genetic Testing , Intellectual Disability/genetics , Methyl-CpG-Binding Protein 2/genetics , Mutation , Phenotype , Rett Syndrome/geneticsABSTRACT
OBJECTIVE@#To analyze the clinical characteristics and pathogenic gene in a Chinese pedigree affected with mitochondrial DNA depletion syndrome 8A (MTDPS8A).@*METHODS@#Whole exome sequencing was carried out for the patient. Sanger sequencing was used to verify the results, and PolyPhen-2 and PROVEAN software were used to predict the impact of amino acid changes on the function of the protein.@*RESULTS@#The patient, a two-month-old female, was admitted to the hospital for poor milk intake and poor mental response. Her clinical manifestations included feeding difficulty, shortness of breath and low muscle tone. Auxiliary laboratory test indicated that the infant was underdeveloped with abnormal liver, kidney, and heart functions accompanied by hyperlacticacidemia. She responded poorly to treatment and eventually died. Sequencing revealed that the child has carried compound heterozygous missense variants of the RRM2B gene, namely c.16delA (p.R6Gfs*22) and c.175G>C (p.A59P), which were respectively inherited from her father and mother, and both were newly discovered pathologic variants.@*CONCLUSION@#The c.16delA and c.175G>C compound heterozygous variants of the RRM2B gene probably underlay the pathogenesis of MTDPS8A. Above finding has strengthened the understanding of the clinical feature and genetic etiology of this disease and expanded the mutation spectrum of the RRM2B gene.
Subject(s)
Child , Female , Humans , Infant , Cell Cycle Proteins , China , DNA, Mitochondrial/genetics , Genetic Testing , Mutation , Pedigree , Ribonucleotide Reductases , Exome SequencingABSTRACT
Objective:To investigate the clinical phenotype and genotype of a male case of subcortical band heterotopia caused by mosaic mutation of DCX gene.Methods:The clinical data and magnetic resonance imaging (MRI) features of a male case of subcortical band heterotopia diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University in August 2020 were analyzed retrospectively. At the same time, the whole exon sequencing of the families was performed by next generation sequencing method, the suspicious mutation was verified by polymerase chain reaction Sanger sequencing, and their genetic mutation characteristics were analyzed.Results:The proband, one male, aged 5 years and 1 month, was hospitalized in August 2020 with the complaint of intermittent convulsions for 4 years and six months. Clinical features included that limb muscle tension was slightly high, intellectual and motor development was backward, and head circumference was 48 cm. MRI of his head showed diffuse thick subcortical band heterotopia. The detection of whole exon sequencing in his family showed that there was hemizygous mosaic mutation in DCX gene (mosaic ratio 44%), c.148A>G (p.k50E). The mosaic ratios of oral mucosa and urinalysis were 38.2% and 44.8% respectively. His parents were wild-type, The mutation found in this patient has not been reported at home and abroad.Conclusions:The mosaic variation of DCX gene can cause subcortical band heterotopia in males. The variation of DCX gene c.148A>G (p.k50E) may be the possible cause of the proband, which expands the variation spectrum of subcortical band heterotopia.
ABSTRACT
Objective:To explore the clinical phenotype and gene characteristics of a case of TSC2/PKD1 adjacency gene syndrome, so as to improve the clinical understanding of the disease.Methods:A case of TSC2/PKD1 adjacency gene syndrome diagnosed in the Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University was analyzed retrospectively. The clinical data, laboratory examination, imaging characteristics and gene variation characteristics of the child were summarized.Results:The patient was a 17 months old girl, with the main complaint of "intermittent convulsion with 17 months of underdevelopment". The clinical manifestations were epileptic seizures, which were in the form of a series of spastic seizures, absence seizures, focal seizures, and depigmentation spots can be seen in the trunk and neck. Cranial magnetic resonance imaging showed multiple patchy signals in the cortex and subcortical areas of the bilateral cerebral hemispheres, multiple small nodular shadows under the ependyma of the bilateral lateral ventricles, the heart color Doppler ultrasound showed patent foramen ovale and pericardial effusion, and the abdomen color Doppler ultrasound showed polycystic kidney. Ophthalmic color Doppler ultrasound showed that there were localized small swelling lesions around the optic disc of the left eye. The whole exon gene sequencing of the pedigree showed the proband had partial deletion of TSC2 gene (NM_000548) at chromosome position chr16: 2125799-2185690. The real-time quantitative detection system verified that exons 23-42 were deleted, and all exons of PKD1 gene were deleted (NM_001009944), and multiple ligation dependent probe amplification verified that exons 1-46 were deleted, and no downstream gene deletion was found. The overall deletion size was about 60 kb. Both of the girl's father and mother had normal phenotypes and were wild-type.Conclusions:TSC2/PKD1 adjacency gene syndrome is relatively rare. It can have clinical manifestations of tuberous sclerosis/autosomal dominant polycystic kidney disease. Most of the nervous system and kidney are seriously affected, and the prognosis is poor. TSC2/PKD1 gene deletion and variation is the genetic cause of the TSC2/PKD1 adjacency gene syndrome.
ABSTRACT
Objective:To investigate the clinical phenotype of a child with Jansen-de Vries syndrome, to clarify its genetic diagnosis and genetic characteristics, and to improve the understanding of this disease.Methods:Clinical data from a child with Jansen-de Vries syndrome diagnosed in the Children′s Affiliated Hospital of Zhengzhou University in October 2019 were collected, using core family-complete exon genomics detection (Trio-WES) and chromosome copy number variation (CNV) analysis techniques for genetic testing for the child and her parents, generation Sanger sequencing for family member verification for possible pathogenic mutations, and clinical and molecular genetic analysis. The relevant reports of PPM1D gene mutation in patients with mental retardation were reviewed.Results:The proband was a 11-month-old girl, presenting with mental retardation, lagging speech and motor development, autistic behavior, gastrointestinal dysfunction, and short stature, low flat nose bridge, low ear, short finger syndrome.Trio-WES results of the core family of the child suggested that PPM1D was a new transcoding heterozygous mutation, PPM1D (NM-003620): c.1216delA (p.Thr406Profs *3), and the karyotype and CNV analysis of the chromosome were normal. Literature retrieval showed currently a total of 18 cases were reported PPM1D gene mutation of mental disorders, described in the online human Mendel database for developmental disorder associated with gastrointestinal dysfunction and pain threshold increases, the age distribution in the seven months to 21 years of age, clinical manifestation of mental retardation, increased pain threshold, abnormal behavior, feeding difficulties, visual impairment, short finger syndrome, a group of syndromes associated with short stature, fever or vomiting, and congenital deformities. Conclusions:Jansen-de Vries syndrome clinically presents mainly with overall retardation (mental retardation/backward delayed motor development, language development, low muscle tone), abnormal behavior (lonely sample behavior, autism), craniofacial malformations (broad forehead, low ear nose bridge, thin upper lip), short finger syndrome (short feet, pinky stubby), gastrointestinal dysfunction (milk overflow, feeding difficulties, constipation). The child was diagnosed as a newly transcoding heterozygous mutation of the PPM1D gene. The current treatment is mainly rehabilitation training, and growth hormone replacement therapy can be given to part of the short height disease. The PPM1D gene [PPM1D(NM-003620): c.1216delA(p.Thr406Profs *3)] is the genetic cause of the child.
ABSTRACT
Objective:To investigate the clinical characteristics and gene mutation of seven cases of CDKL5 gene related early-onset epileptic encephalopathy diagnosed by next-generation sequencing.Methods:The clinical data of children with early-onset epileptic encephalopathy from February 2018 to December 2019 in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University were retrospectively analyzed. The whole exome sequencing method was used to analyze the entire exome of the proband, and seven cases of CDKL5 gene mutation positive were screened out, and Sanger sequencing verification on family members was performed to identify the source and the characteristics of gene mutations were analyzed.Results:Among the seven children diagnosed with CDKL5 gene related early-onset epileptic encephalopathy, the ratio of male to female was 2∶5, and the age of onset was 15 days to five months of birth. The clinical phenotypes all included different degrees of developmental delay and repeated seizures, which were manifested as general seizures, myoclonic seizures, convulsive seizures or focal seizures; the outcome of use of antiepileptic drugs to control seizures was poor, and some applications of ketogenic diet had better effects. CDKL5 gene mutation sites were all denovo mutations, including NM_003159: c.772_776del (p.K258Efs *10) frameshift mutation, NM_003159.2 (exon: 9-15) heterozygous deletion, CDKL5 hemizygous deletion, NM_003159: c.268 (exon5) G>T (p.E90 *, 941) and NM_003159: c.2578C>T (p.Q860 *, 171) nonsense mutation, NM_003159: c.211A>G (p.Asn71Asp) and NM_001323289: c.545T>C (p.L182P) missense mutation. Among them, c.772_776del (p.K258Efs *10), c.268 (exon5)G>T and c.2578C>T (p.Q860 *, 171) have not been reported. Conclusions:CDKL5 gene related early-onset epileptic encephalopathy is an early onset epilepsy, which is more common in women, and has different forms of seizures. The early electroencephalogram is characterized as severe abnormal brain discharge, and the disease progresses in various forms. There are no specific changes in head magnetic resonance imaging. Different gene mutation sites may lead to different phenotypes and prognostic differences. Many anti-epileptic treatments are ineffective, and ketogenic diets are effective for some patients.
ABSTRACT
Objective:To investigate the clinical phenotypes, therapy and genetic features of aldehyde dehydrogenase 7 family member A1 (ALDH7A1) gene mutations in five cases of pyridoxine dependent epilepsy (PDE) with diagnosis confirmed by next generation sequencing.Methods:Retrospective analysis was carried out on clinical data of five cases of PDE children with early epilepsy onset who were treated in the Department of Neurology of Children′s Hospital Affiliated to Zhengzhou University from February 2018 to November 2019. Next generation sequencing approach was used for genetic sequencing of proband ALDH7A1 gene and the first generation Sanger was used for validation of family members. And the characteristics of gene mutations were analyzed.Results:Among the five children diagnosed with PDE, the male to female ratio was 4 ∶ 1 and ages at clinic visit ranged from two months to 10 months old. In clinical phenotypes, all five cases experienced onset in neonatal period, with repeated seizures, manifested as myoclonus, spasms or focal paroxysm. The administration of antiepileptic drugs performed poorly in seizure control while long term oral intake of large dose pyridoxine showed better efficacy. All the five cases of children came from compound heterozygous mutations of father and mother, i.e. slicing homozygous mutation c.247-2(IVS2)A>T, missense mutation c.584A>G (p.N195S) and nonsense mutation c.1003C>T(p.R335 *), missense mutation c.1553G>C(p.R518T) and c.1547A>G(p.Y516C), missense mutation c.1547A>G(p.Y516C) and frameshift mutation c.1566_1568delTAC, missense mutation c.1061A>G(p.Y354C) and nonsense mutation c.841C>T(p.Q281X, 259), among which c.247-2(IVS2)A>T was novel splicing site mutation not reported before. Conclusions:PDE is induced by ALDH7A gene mutation. Early clinical manifestations are mostly onset of refractory epilepsy in neonatal period. Antiepileptic drugs perform poorly in terms of efficacy while pyridoxine can control seizure effectively. Gene analysis should be conducted on such patients for confirmed diagnosis.
ABSTRACT
Objective:To analyze the clinical and imaging characteristics of acute necrotic encephalopathy (ANE) in a child with human herpesvirus-6 (HHV-6) infection.Methods:Retrospective analysis was performed on the clinical data and imaging features of a case of HHV-6 related ANE from Children′s Hospital Affiliated to Zhengzhou University in March 2019.Results:The one year and seven month-old child had acute encephalopathy, recurrent convulsions, consciousness disorders, elevated serum transaminase. The number of cerebrospinal fluid (CSF) cells was normal and the protein increased. High throughput gene testing of CSF showed HHV-6. Cranial magnetic resonance imaging showed multiple symmetry damage in the bilateral thalamus, brainstem, and cerebellum. The symptoms improved after the treatment of glucocorticoids, intravenous immunoglobulin, and plasmapheresis.Conclusions:ANE is a rare severe encephalopathy, the characteristic imaging change of which is symmetry multifocal cerebral damage, especially in the bilateral thalamus. ANE should be considered for patients with frequent convulsions and disturbance of consciousness after virus infection.
ABSTRACT
Objective:To report a rare case of early onset epileptic encephalopathy caused by YWHAG gene mutation, and discuss the clinical and genetic characteristics as well as the diagnosis, treatment and prognosis of the disease.Methods:Clinical data of the patient with YWHAG gene deficiency from Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University were collected in January 2018. The whole exome sequencing was performed on the core members of the family, and the characteristics of gene mutations were analyzed.Results:The proband is a girl, three years and 10 months old, presented to the outpatient department of neurology with a history of six-month intermittent convulsions, manifested as epilepsy seizures, mental retardation, motor delay and gait instability, ataxia. The brain magnetic resonance imaging showed myelinated dysplasia, and long-term video electroencephalogram (EEG) showed extensive 1.5-3.0 Hz slow spikes, and multiple spikes during sleep. During the monitoring, the children had clinical seizures and abnormal EEG discharges, indicating that myoclonus was accompanied by atypical absence of consciousness. Whole exome sequencing on the proband detected a de novo mutation c.169C>T (p.Arg57Cys) in YWHAG gene. According to American College of Medical Genetics guidelines (2015), the mutation was considered potentially pathogenic.Conclusion:Early epileptic encephalopathy caused by YWHAG gene mutation is very rare, and the variation of YWHAG gene c.169C>T is the possible pathogenic variation of the genetic cause of early onset epileptic encephalopathy in the proband.
ABSTRACT
OBJECTIVE@#To investigate the clinical phenotype and genetic characteristics of a patient with hypohidrotic ectodermal dysplasia (HED) due to partial deletion of EDA gene.@*METHODS@#The child has presented with HED complicated with epilepsy. Family trio whole exome sequencing (Trio-WES), copy number variation sequencing (CNV-seq), and karyotype analysis were carried out to explore the underlying genetic etiology.@*RESULTS@#The proband, a 7-year-and-8-month-old boy, presented with thin curly hair, thin and sparse eyebrow, xerosis cutis, susceptibility to hyperthermia from childhood, hypohidrosis, sharp/sparse/absent teeth, saddle nose, prominent forehead, auricle adulation and seizure. He was found to have a normal chromosomal karyotype, and no abnormality was found by Trio-WES. Genome-wide CNV-seq revealed a 341.90 kb deletion at Xq13.1q13.1 (chrX: 68 796 566-69 138 468). As verified by PCR-electrophoresis, the deletion has removed part of the EDA gene. The deletion was derived from his mother with normal hair, mild xerosis cutis, and sparse, decidulated and nail-like teeth. The mother was detected with a heterozygous 242.10 kb deletion at Xq13.1q13.1 (chrX: 68 836 154-69 078 250).@*CONCLUSION@#Both the proband and his mother have carried a Xq13.1 microdeletion involving part of the EDA gene. The clinical phenotypes of the mother and the proband were consistent with the clinical characteristics of X-linked recessive HED, for which partial deletion of the EDA gene is probably accountable.
Subject(s)
Child , Humans , Male , DNA Copy Number Variations , Ectodermal Dysplasia , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodysplasins/genetics , PhenotypeABSTRACT
Objective:To understand the early clinical characteristics and drug sensitivity results of children died of invasive pneumococcal disease (IPD) in Pediatric Intensive Care Unit (PICU) so as to guide the early clinical identification and treatment.Methods:The early clinical data and drug sensitivity result of children died of IPD in PICU of the Children′s Hospital, Zhengzhou University and Beijing Children′s Hospital, Capital Medical University from May 2015 to May 2019 were retrospectively analyzed.Results:A total of 18 children meeting the criteria were enrolled, including 6 males and 12 females.The median age was 1 year and 9 months (ranged from 2 months and 20 days to 6 years and 7 months), there were 2 cases(11.1%) > 5 years old, and 16 cases(88.9%)≤ 5 years old.There were 17(94.4%) children related to community acquired infection.Among 18 cases, the first symptom was intracranial infection in 10 cases (55.6%), bloodstream infection in 4 cases (22.2%), and pulmonary infection in 3 cases (16.7%). There were 5 cases complicated with virus infection at the same time.Auxiliary examination: all of the 18 cases had anemia and hypoalbuminemia, and 15 cases(93.8%) had HCO 3- reduction.White blood cells(WBC), platelets(PLT) and natural killer (NK) cell decreased in 7 cases (7/18 cases), 12 cases (12/18 cases) and 6 cases (5/16 cases), respectively, but C-reactive protein(CRP), procalcitonin (PCT), lactic acid concentration(LAC), D-dimer (D-Di), international normalized ratio (INR) and B-type natriuretic peptide (BNP) were increased in 12 cases (12/18 cases), 14 cases (14/18 cases), 7 cases (7/17 cases), 14 cases (14/17 cases) and 9 cases (9/9 cases), respectively.Six children(33.3%) did not receive the treatment of sensitive antibiotics before admission.According to the drug sensitivity results: all the 18 strains had multiple-drug resistance(MDR), and the resistance rates of Penicillin, Erythromycin, Tetracycline, Clindamycin and Sulfamethoxazole were 22.2%, 100.0%, 100.0%, 100.0% and 94.4%, respectively, all the strains were sensitive to Vancomycin, Linezolid and Levofloxacin. Conclusions:Most of the children died of IPD in PICU are of community-acquired infection and less than 5 years old.Anemia and hypoalbuminemia are common in the dead children.The decreased in HCO 3- and increased PCT, LAC and D-Di in the early stage might be related to poor prognosis of patients.Most of the children died of IPD are infected with MDR strains.
ABSTRACT
OBJECTIVE@#To delineate the nature and origin of chromosomal aberration in a girl with mental retardation.@*METHODS@#Genomic DNA was analyzed by using single nucleotide polymorphism-based array (SNP array). The proband and her parents were subjected to routine G-banded chromosomal karyotyping analysis.@*RESULTS@#SNP array has identified a 1.2 Mb microdeletion at 10p15.3 and a duplication at 18p11.21-pter in the proband. The patient was also found to harbor a structural aberration involving 10p. The karyotype of her father was 46,XY,t(10;18)(p15;p11.2), while her mother was found to be normal.@*CONCLUSION@#The structural aberration of 10p carried by the patient has derived from her father whom has carried a balanced translocation of t(10;18). Her karyotype was finally determined as 46,XX,der(10)t(10;18)(p15;p11.2)pat. The abnormal phenotype of the patient can probably be attributed to the presence of 10p15.3 microdeletion and 18p11.21-pter duplication.
ABSTRACT
Objective:To investigate the clinical phenotype and summarize the genetic characteristics of children with neurofibromatosis type 1 (NF1) diagnosed by next-generation sequencing.Methods:The clinical data of 12 children with NF1 who were admitted to the Department of Neurology of the Children's Hospital Affiliated to Zhengzhou University from December 2017 to October 2019 were retrospectively analyzed. The next-generation sequencing method was used to sequence the NF1 gene of the probands and the mutations were verified by PCR-Sanger sequencing.Results:Among the 12 children diagnosed with NF1 (male: female=11: 1), who aged from seven months to 11 years old, the main complaints were seizures and skin with café-au-lait spots. Five children were found with freckles in axillae, and two with cutaneous neurofibroma. Six cases had seizures, two children suffered spastic seizures, two with generalized tonic-clonic seizures, one with typical absence seizure, one with focal seizure, one case had severe headache and vomiting. Fortunately for the children with seizures, anti-epileptic drugs had a good prognosis. There were five mutation types detected in 12 cases, including one case of loss of overall heterozygosity in NF1 gene; three missense mutations: c.7867C>A (p.L2623I), c.7855C>A (p.L2619I) and c.7792C>A(p.L2598I); three frameshift mutations: c.3162delC(p.N1054Nfs *8), c.540dupA (p.Q181Tfs *20) and c.2027dupA(p.V679Pfs *21); three nonsense mutations: c.1467T>A(p.Y489X, 2351), c.1318C>T(p.R440X, 2400) and c.1411C>T(p.K471X, 2369); two splicing mutations: c.2326-2(IVS10)G>C and c.1186-1(IVS10)G>C. Nine children were found with spontaneous mutations, one case was inherited from the father, and two cases were inherited from the mother. c.7867C>A(p.L2623I), c.7855C>A(p.L2619I), c.3162delC(p.N1054Nfs *8), c.1411C>T(p.K471X, 2369), c.2326-2(IVS10)G>C, c.1186-1(IVS10)G>C were unreported mutations in literature. Conclusions:NF1 is caused by NF1 gene mutation. The early clinical manifestations of children with NF1 defect presented with café-au-lait spots, and some suffered seizures. For patients with multiple café-au-lait spots and seizures in the clinic, genetic analysis should be performed as soon as possible to confirm the diagnosis.
ABSTRACT
Objective:To investigate the clinical manifestation, genetic characteristics, treatment and prognosis of Crouzon-like syndrome.Methods:Clinical data of one case of Crouzon-like syndrome diagnosed in Children′s Hospital Affiliated to Zhengzhou University in May 2019 were collected, including clinical test, treatment plan, follow-up outcomes. The clinical characteristics and the mutation characteristics of IL11RA-related Crouzon-like syndrome were analyzed combined with the literature.Results:The male proband, five years and four months old, was admitted with the main clinical manifestations including headache, vomiting, exophthalmos, ocular hypertelorism, nasal root flat and scaphocephaly. CT showed that the cerebellar tonsil moved down slightly, the occipital magnum was full, the bilateral cranial plates were locally thinner, the bilateral cranial diameters were increased, and the cranial seams were closed. Magnetic resonance imaging showed ChiariⅠmalformation. The mutation c.40_63del and splice site mutation c.811-2A>G of the patient′s IL11RA gene were screened by whole exome sequencing. Sanger sequencing showed that the mutations are compound heterozygous and both are first reported. The mutation c.811-2A>G was derived from the patient′s mother, and the other one is de novo.Conclusions:The main clinical manifestations of Crouzon-like syndrome are craniosynostosis and midface hypoplasia and ocular deformity. The study identified two novel mutations in the Crouzon-like syndrome related IL11RA gene. Genetic sequencing is helpful for accurate diagnosis and timely surgical treatment.