1.A Frameshift Variant in the SEMA6B Gene Causes Global Developmental Delay and Febrile Seizures.
Li SHU ; Yuchen XU ; Qi TIAN ; Yuanyuan CHEN ; Yaqin WANG ; Hui XI ; Hua WANG ; Neng XIAO ; Xiao MAO
Neuroscience Bulletin 2021;37(9):1357-1360
2.A case of 16p13.11 microdeletion syndrome with febrile convulsion as the main manifestation.
Ting WU ; Li'na LIAO ; Xiaoping JIANG ; Jianrong LIU ; Wangyang CHEN ; Min SHENG ; Ning GUO
Chinese Journal of Medical Genetics 2021;38(10):981-984
OBJECTIVE:
To explore the genetic basis for a girl with febrile convulsion as the main manifestation.
METHODS:
The child was subjected to whole exome sequencing (WES) and copy number variation sequencing(CNV-seq). Fluorescence quantitative PCR was carried out to validate the microdeletion in her family.
RESULTS:
The 7-year-old girl was diagnosed with febrile convulsion (complex type) for having fever for 3 days, mild cough and low thermal convulsion once. Her father, mother and aunt also had a history of febrile convulsion. A heterozygous deletion with a size of approximately 1.5 Mb was detected in the 16p13.11 region by WES and CNV-seq. The deletion has derived from her father and was confirmed by fluorescence quantitative PCR.
CONCLUSION
16p13.11 microdeletion syndrome has significant clinical heterogeneity. Different from those with epilepsy, mental retardation, autism, multiple malformations, carriers of 16p13.11 deletion may only manifest with febrile convulsion. Deletion of certain gene(s) from the region may be related to febrile convulsion and underlay the symptom of this child.
Child
;
DNA Copy Number Variations
;
Epilepsy
;
Female
;
Humans
;
Seizures/genetics*
;
Seizures, Febrile/genetics*
;
Whole Exome Sequencing
3.STXBP1 gene mutation in newborns with refractory seizures.
Li-Li LIU ; Xin-Lin HOU ; Cong-Le ZHOU ; Ze-Zhong TANG ; Xin-Hua BAO ; Yi JIANG
Chinese Journal of Contemporary Pediatrics 2014;16(7):701-704
OBJECTIVETo study the relationship between STXBP1 gene mutations and refractory seizures with unknown causes in newborns.
METHODSThe coding region of STXBP1 gene was detected using direct Sanger sequencing in 11 newborns with refractory seizures of unknown causes.
RESULTSSTXBP1 gene mutation was found in 1 out of 11 patients. It was a missense mutation: c.1439C>T (p.P480L).
CONCLUSIONSSTXBP1 gene mutation can be found in neonatal refractory seizures of unknown causes, suggesting a new approach of further research of this disease.
Humans ; Infant, Newborn ; Munc18 Proteins ; genetics ; Mutation ; Seizures ; genetics
4.Clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children.
Chong-Yuan LAI ; Rui-Hua CHEN ; Chun-Lan ZHONG ; Ming-Ming JI ; Bing-Fei LI
Chinese Journal of Contemporary Pediatrics 2022;24(5):585-590
OBJECTIVES:
To study the clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children.
METHODS:
The medical data of 200 children with epilepsy who underwent a genetic analysis of epilepsy by the whole exon sequencing technology were collected retrospectively, of whom 9 children with epilepsy had 16p11.2 microdeletion. The clinical phenotype and genetic features of the 9 children with 16p11.2 microdeletion were analyzed.
RESULTS:
The detection rate of 16p11.2 microdeletion was 4.5% (9/200). The 9 children with 16p11.2 microdeletion were 3-10 months old. They experienced focal motor seizures with consciousness disturbance, and some of the seizures developed into generalized tonic-clonic seizures. The interictal electroencephalogram showed focal or multifocal epileptiform discharge, and all 9 children responded well to antiepileptic drugs. The 9 children had a 16p11.2 deletion fragment size of 398-906 kb, and the number of deleted genes was 23-33 which were all pathogenic mutations. The mutation was of maternal origin in 2 children, of paternal origin in 1 child, and de novo in the other children.
CONCLUSIONS
16p11.2 microdeletion can be detected in some children with epilepsy. Most of the 16p11.2 microdeletion is de novo mutation and large gene fragment deletion. The onset of 16p11.2 microdeletion-related epilepsy in children is mostly within 1 year of life, and the epilepsy is drug-responsive.
Anticonvulsants
;
Epilepsy/genetics*
;
Humans
;
Phenotype
;
Retrospective Studies
;
Seizures/genetics*
5.De novo variant of CSNK2B causes Poirier-Bienvenu neurodevelopmental syndrome: two case report.
Jia ZHANG ; Yang LI ; Huan LUO ; YaJun SHEN ; Meng YUAN ; Zuozhen YANG ; Jing GAN
Chinese Journal of Medical Genetics 2022;39(5):484-487
OBJECTIVE:
To analyze the clinical characteristics and CSNK2B gene variant of 2 children with Poirier-Bienvenu neurodevelopmental syndrome, and to identify the possible pathogenic causes and provide evidence for clinical diagnosis.
METHODS:
Two children with Poirier-Bienvenu neurodevelopmental syndrome were selected from West China Second University Hospital, Sichuan University. The clinical manifestations, laboratory examination and CSNK2B gene variant were analyzed.
RESULTS:
The main manifestations of 2 children were epilepsy, motor or intellectual retardation. Whole exon sequencing showed that CSNK2B gene c. 291+4A>T heterozygous splicing variant was found in case one, and CSNK2B copy number variation(CNV) was lost in case two. Case one received no special treatment, followed up for 8+ months, seizures and motor development were improved; case two had recurrent seizures for 9+ years, and received levetiracetam and clonazepam antiepileptic treatment. No seizures have occurred for 2 years now, and a large number of epileptic discharges can still be seen in video electroencephalogram (VEEG) with slightly backward intelligence and language development.
CONCLUSION
Our study further proves that the pathogenic variant of CSNK2B is related to epilepsy with developmental disorder, and enrich is the CSNK2B gene variant spectrum. The pathogenesis of CSNK2B has great clinical heterogeneity, with great difference in severity of nervous system injury and different prognosis, and agenesis of corpus callosum may be one of its clinical phenotypes.
Child
;
DNA Copy Number Variations
;
Developmental Disabilities/genetics*
;
Epilepsy/genetics*
;
Humans
;
Intellectual Disability/genetics*
;
Seizures/genetics*
6.New variants in FLNA gene cause periventricular nodular heterotopia and epileptic seizure in three cases.
Mi CAO ; Chao LIU ; Zihan WEI ; Xiaozhi QIAO ; Yanchun DENG
Chinese Journal of Medical Genetics 2021;38(7):626-630
OBJECTIVE:
To explore the genetic bases of 3 patients with periventricular nodular heterotopia and epileptic seizure.
METHODS:
The clinical data of three patients presenting with periventricular nodular ectopic with epileptic seizure were analyzed. Whole exome sequencing (WES) was performed on the patients, and Sanger sequencing was used to validate the suspected variants.
RESULTS:
In three female patients, head MRI showed nodular gray matter ectopic in the bilateral ventricle. WES identified the heterozygous c.2720del T(p.Leu907Argfs*39) variant of FLNA gene in case 1 and her mother (case 2), and heterozygous c.1387_1390del GTGC(p.Val463Profs*34) of FLNA gene in case 3. According to the American College of Medical Genetics and Genomics standards and guidelines, the c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC (p.Val463Profs*34) variants of FLNA gene were predicted to be pathogenic (PVS1+PM2+PP1) and likely pathogenic(PVS1+PM2), respectively.
CONCLUSION
The c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC(p.Val463Profs*34) variants of FLNA gene may be the genetic cause of the three patients.
Epilepsy/genetics*
;
Female
;
Filamins/genetics*
;
Heterozygote
;
Humans
;
Magnetic Resonance Imaging
;
Mutation
;
Periventricular Nodular Heterotopia/genetics*
;
Seizures
7.Analysis of clinical phenotype and SCN1A gene variant in a pedigree affected with genetic epilepsy with febrile seizures.
Shaoxia SUN ; Xiaoling LI ; Jiguo SONG ; Yufen LI ; Liyun XU ; Bing XIA ; Ying HUA ; Liping ZHU ; Junlin WANG
Chinese Journal of Medical Genetics 2021;38(8):745-748
OBJECTIVE:
To explore the genetic basis for a Chinese pedigree affected with genetic epilepsy with febrile seizures plus (GEFS+).
METHODS:
Clinical data of the proband and his family members were collected. Following extraction of genomic DNA, the proband was subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing of the proband and other family members.
RESULTS:
The pedigree, including 6 patients with febrile seizures from 3 generations, was diagnosed with typical GEFS+. Among them, 2 had febrile seizures (FS), 1 had febrile seizures plus (FS+), and 3 had febrile seizures with focal seizures. High-throughput sequencing revealed that the proband has carried a heterozygous missense variant of c.4522T>A (p.Tyr1508Asn) of the SCN1A gene. Sanger sequencing confirmed that other five patients and one normal member from the pedigree have also carried the same variant, which yielded a penetrance of 85.7%.
CONCLUSION
The c.4522T>A (p.Tyr1508Asn) of the SCN1A gene probably underlay the disease in this pedigree. The pattern of inheritance was consistent with autosomal dominant inheritance with incomplete penetrance. Above finding has enriched the variant spectrum of the SCN1A gene.
Epilepsy/genetics*
;
Humans
;
NAV1.1 Voltage-Gated Sodium Channel/genetics*
;
Pedigree
;
Phenotype
;
Seizures, Febrile/genetics*
8.Early identification and diagnosis of epilepsy related to fever sensitivity.
Chinese Journal of Contemporary Pediatrics 2021;23(7):749-754
Febrile seizures are the most common nervous system disease in childhood, and most children have a good prognosis. However, some epilepsy cases are easily induced by fever and are characterized by "fever sensitivity", and it is difficult to differentiate such cases from febrile seizures. Epilepsy related to fever sensitivity includes hereditary epilepsy with febrile seizures plus, Dravet syndrome, and
Cadherins/genetics*
;
Child
;
Epilepsy/genetics*
;
Epileptic Syndromes
;
Humans
;
Mutation
;
Seizures, Febrile/genetics*
9.A case of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures caused by PHF21A gene variation and review of literature.
Fan WU ; Xin Na JI ; Meng Xiao SHEN ; Yan Yan GAO ; Ping Ping ZHANG ; Shu Pin LI ; Qian CHEN
Chinese Journal of Pediatrics 2023;61(8):726-730
Objective: To discuss the clinical and genetic features of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). Methods: The clinical and genetic records of a patient who was diagnosed with IDDBCS caused by PHF21A gene variation at Children's Hospital Capital Institute of Pediatrics in 2021 were collected retrospectively. Using " PHF21A gene" as the keyword, relevant articles were searched at CNKI, Wanfang Data and PubMed from establishment of databases to February 2023. Clinical and genetic features of IDDBCS were summarized in the combination of this case. Results: An 8 months of age boy showed overgrowth (height, weight and head circumference were all higher than the 97th percentile of children of the same age and sex) and language and motor developmental delay after birth, and gradually showed autism-like symptoms like stereotyped behavior and poor eye contact. At 8 months of age, he began to show epileptic seizures, which were in the form of a series of spastic seizures with no reaction to adrenocorticotropic hormone but a good response to vigabatrin. Physical examination showed special craniofacial appearances including a prominent high forehead, sparse eyebrows, broad nasal bridge, and downturned mouth with a tent-shaped upper lip. The patient also manifested hypotonia. Whole exome sequencing showed a de novo heterogeneous variant, PHF21A (NM_001101802.1): c.54+1G>A, and IDDBCS was diagnosed. A total of 6 articles (all English articles) were collected, involving this case and other 14 patients of IDDBCS caused by PHF21A gene variation. Clinical manifestations were intellectual disability or developmental delay (15 patients), craniofacial anomalies (15 patients), behavioral abnormalities (12 patients), seizures (9 patients), and overgrowth (8 patients). The main pathogenic variations were frameshift variations (8 patients). Conclusions: IDDBCS should be considered when patients show nervous developmental abnormalities, craniofacial anomalies, seizures and overgrowth. PHF21A gene variation detection helps to make a definite diagnosis.
Male
;
Humans
;
Child
;
Intellectual Disability/genetics*
;
Developmental Disabilities/genetics*
;
Retrospective Studies
;
Seizures/genetics*
;
Craniofacial Abnormalities/genetics*
;
Histone Deacetylases/genetics*
10.Penetrance estimation of PRRT2 variants in paroxysmal kinesigenic dyskinesia and infantile convulsions.
Yulan CHEN ; Dianfu CHEN ; Shaoyun ZHAO ; Gonglu LIU ; Hongfu LI ; Zhi-Ying WU
Frontiers of Medicine 2021;15(6):877-886
Proline-rich transmembrane protein 2 (PRRT2) is the leading cause of paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), and infantile convulsions with choreoathetosis (ICCA). Reduced penetrance of PRRT2 has been observed in previous studies, whereas the exact penetrance has not been evaluated well. The objective of this study was to estimate the penetrance of PRRT2 and determine its influencing factors. We screened 222 PKD index patients and their available relatives, identified 39 families with pathogenic or likely pathogenic (P/LP) PRRT2 variants via Sanger sequencing, and obtained 184 PKD/BFIE/ICCA families with P/LP PRRT2 variants from the literature. Penetrance was estimated as the proportion of affected variant carriers. PRRT2 penetrance estimate was 77.6% (95% confidence interval (CI) 74.5%-80.7%) in relatives and 74.5% (95% CI 70.2%-78.8%) in obligate carriers. In addition, we first observed that penetrance was higher in truncated than in non-truncated variants (75.8% versus 50.0%, P = 0.01), higher in Asian than in Caucasian carriers (81.5% versus 68.5%, P = 0.004), and exhibited no difference in gender or parental transmission. Our results are meaningful for genetic counseling, implying that approximately three-quarters of PRRT2 variant carriers will develop PRRT2-related disorders, with patients from Asia or carrying truncated variants at a higher risk.
Dystonia
;
Epilepsy, Benign Neonatal/genetics*
;
Humans
;
Membrane Proteins/genetics*
;
Mutation
;
Nerve Tissue Proteins/genetics*
;
Pedigree
;
Penetrance
;
Seizures/genetics*