scholarly journals SYN1 Mutation Causes X-Linked Toothbrushing Epilepsy in a Chinese Family

2021 ◽  
Vol 12 ◽  
Author(s):  
Qin Zhou ◽  
Jingwei Wang ◽  
Li Xia ◽  
Rong Li ◽  
Qiumin Zhang ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Complex Form ◽  
In Silico Analysis ◽  
Epileptic Seizures ◽  
Mutant Gene ◽  
Disease Diagnosis ◽  
Chinese Family ◽  
Genetic Profile ◽  
Reflex Epilepsy ◽  
Maternal Uncle

Toothbrushing epilepsy is a rare form of reflex epilepsy (RE) with sporadic incidence. To characterize the genetic profile of reflex epilepsy patients with tooth brushing-induced seizures in a Chinese family. Solo clinical whole-exome sequencing (WES) of the proband, a 37-year-old Chinese man, was performed to characterize the genetic etiology of toothbrushing epilepsy. Mutations in the maternal X-linked synapsin 1 (SYN1) identified in the proband and his family members were confirmed by Sanger sequencing. The pathogenicity of these mutations was determined using in silico analysis. The proband had four episodes of toothbrushing-induced seizures. The semiology included nausea, twitching of the right side of the mouth and face, followed by a generalized tonic-clonic seizure (GTCS). The proband's elder maternal uncle had three toothbrushing-induced epileptic seizures at the age of 26. The proband's younger maternal uncle had no history of epileptic seizures but had a learning disability and aggressive tendencies. We identified a deleterious nonsense mutation, c.1807C>T (p.Q603Ter), in exon 12 of the SYN1 gene (NM_006950), which can result in a truncated SYN1 phosphoprotein with altered flexibility and hydropathicity. This novel mutation has not been reported in the 1000G, EVS, ExAC, gnomAD, or HGMD databases. We identified a novel X-linked SYN1 exon 12 mutant gene in a Chinese family with toothbrushing epilepsy. Our findings provide novel insights into the mechanism of this complex form of reflex epilepsy that could potentially be applied in disease diagnosis.

scholarly journals A Novel Mutation of Notch homolog protein 2 gene in a Chinese Family with Hajdu-Cheney Syndrome

2017 ◽  
Vol 130 (23) ◽  
pp. 2883-2884 ◽  
Author(s):  
Ruo-Lan Gong ◽  
Jing Wu ◽  
Tong-Xin Chen
Keyword(s):  
Novel Mutation ◽  
Chinese Family

scholarly journals Novel compound heterozygous EYS variants may be associated with arRP in a large Chinese pedigree

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Chunli Wei ◽  
Ting Xiao ◽  
Jingliang Cheng ◽  
Jiewen Fu ◽  
Qi Zhou ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Gene Mutations ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
The Novel ◽  
Pathogenic Variants ◽  
Pathogenic Genes ◽  
Compound Heterozygous Variants ◽  
Normal Controls

Abstract As a genetically heterogeneous ocular dystrophy, gene mutations with autosomal recessive retinitis pigmentosa (arRP) in patients have not been well described. We aimed to detect the disease-causing genes and variants in a Chinese arRP family. In the present study, a large Chinese pedigree consisting of 31 members including a proband and another two patients was recruited; clinical examinations were conducted; next-generation sequencing using a gene panel was used for identifying pathogenic genes, and Sanger sequencing was performed for verification of mutations. Novel compound heterozygous variants c.G2504A (p.C835Y) and c.G6557A (p.G2186E) for the EYS gene were identified, which co-segregated with the clinical RP phenotypes. Sequencing of 100 ethnically matched normal controls didn’t found these mutations in EYS. Therefore, our study identified pathogenic variants in EYS that may cause arRP in this Chinese family. This is the first study to reveal the novel mutation in the EYS gene (c.G2504A, p.C835Y), extending its mutation spectrum. Thus, the EYS c.G2504A (p.C835Y) and c.G6557A (p.G2186E) variants may be the disease-causing missense mutations for RP in this large arRP family. These findings should be helpful for molecular diagnosis, genetic counseling and clinical management of arRP disease.

scholarly journals A Novel COMP Mutated Allele Identified in a Chinese Family with Pseudoachondroplasia

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Bing-Bing Guo ◽  
Jie-Yuan Jin ◽  
Zhuang-Zhuang Yuan ◽  
Lei Zeng ◽  
Rong Xiang
Keyword(s):  
Extracellular Matrix ◽  
Cartilage Oligomeric Matrix Protein ◽  
Matrix Protein ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Chinese Family ◽  
The Novel ◽  
Structure Model ◽  
Whole Exome ◽  
Nucleotide Mutation

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia with an estimated incidence of ~1/60000 that is characterized by disproportionate short stature, brachydactyly, joint laxity, and early-onset osteoarthritis. COMP encodes the cartilage oligomeric matrix protein, which is expressed predominantly in the extracellular matrix (ECM) surrounding the cells that make up cartilage, ligaments, and tendons. Mutations in COMP are known to give rise to PSACH. In this study, we identified a novel nucleotide mutation (NM_000095.2: c.1317C>G, p.D439E) in COMP responsible for PSACH in a Chinese family by employing whole-exome sequencing (WES) and built the structure model of the mutant protein to clarify its pathogenicity. The novel mutation cosegregated with the affected individuals. Our study expands the spectrum of COMP mutations and further provides additional genetic testing information for other PSACH patients.

scholarly journals Central Precocious Puberty in a Girl and Early Puberty in Her Brother Caused by a Novel Mutation in the MKRN3 Gene

2014 ◽  
Vol 99 (4) ◽  
pp. E647-E651 ◽  
Author(s):  
Nikolaos Settas ◽  
Catherine Dacou-Voutetakis ◽  
Maria Karantza ◽  
Christina Kanaka-Gantenbein ◽  
George P. Chrousos ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Novel Mutation ◽  
Structural Alignment ◽  
In Silico Analysis ◽  
Missense Variant ◽  
Central Precocious Puberty ◽  
Dimensional Structure ◽  
Sex Characteristics ◽  
Coding Region ◽  
Early Puberty

Context: Central precocious puberty (CPP), defined as the development of secondary sex characteristics prior to age 8 years in girls and 9 years in boys, results from the premature activation of the hypothalamic-pituitary-gonadal axis. Mutations in the imprinted gene MKRN3 have been recently implicated in familial cases of CPP. Objective: The objective of the study was to uncover the genetic cause of CPP in a family with two affected siblings. Design and participants: The entire coding region of the paternally expressed MKRN3 gene was sequenced in two siblings, a girl with CPP and her brother with early puberty, their parents, and their grandparents. Results: A novel heterozygous missense variant in the MKRN3 gene (p.C340G) was detected in the two affected siblings, their unaffected father, and the paternal grandmother. As expected, the mutated allele followed an imprinted mode of inheritance within the affected family. In silico analysis predicts the mutation as possibly damaging in all five software packages used. Furthermore, structural alignment of the ab initio native and mutant MKRN3 models predicts that the p.C340G mutation leads to significant structural perturbations in the 3-dimensional structure of the C3HC4 really interesting new gene motif of the protein, further emphasizing the functional implications of the novel MKRN3 alteration. Conclusions: We report a novel MKRN3 mutation (p.C340G) in a girl with CPP and her brother with early puberty. MKRN3 alterations should be suspected in all cases with familial CPP or early puberty, especially if male patients are also involved or the precocious puberty trend does not follow the usually observed mother-to-daughter inheritance.

scholarly journals A novel mutation in the conserved sequence of vascular endothelial growth factor receptor 3 leads to primary lymphoedema

2018 ◽  
Vol 46 (8) ◽  
pp. 3162-3171 ◽  
Author(s):  
Ting Dai ◽  
Bohan Li ◽  
Bo He ◽  
Liwei Yan ◽  
Liqiang Gu ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Novel Mutation ◽  
Family Members ◽  
Growth Factor Receptor ◽  
Chinese Family ◽  
Vascular Endothelial ◽  
Healthy Controls ◽  
Endothelial Growth Factor ◽  
Congenital Lymphoedema

Objective To investigate whether lymphoedema in a Chinese family showed the hereditary and clinical characteristics of Milroy disease, an autosomal dominant form of congenital lymphoedema, typically characterized by chronic lower limb tissue swelling due to abnormal lymphatic vasculature development, and to perform mutational analyses of vascular endothelial growth factor receptor ( VEGFR)3. Methods Individuals from a three-generation family affected by congenital lymphoedema were clinically assessed for Milroy disease. Mutation analysis of VEGFR3 was performed using DNA from family members and healthy controls. Results Out of 20 family members, eight were diagnosed with hereditary lymphoedema. Mutation analyses revealed a novel mutation site for c.3163 G>A, resulting in a p.1055D>N mutation in the second tyrosine kinase domain of VEGFR3, which was present in affected individuals only (absent in all unaffected family members and 130 healthy controls). Computed functional analyses showed the mutation may lead to structural alterations with a probability of 0.99999 of being disease causing. Conclusion A novel mutation associated with Milroy disease was identified in a Chinese family, expanding our knowledge of VEGFR3 gene function and providing a potential molecular target for treating hereditary lymphoedema.

PHKG2 mutation spectrum in glycogen storage disease type IXc: a case report and review of the literature

2018 ◽  
Vol 31 (3) ◽  
pp. 331-338 ◽  
Author(s):  
Chunyun Li ◽  
Lihua Huang ◽  
Lang Tian ◽  
Jia Chen ◽  
Shentang Li ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Novel Mutation ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Mutation Spectrum ◽  
Chinese Family ◽  
Phosphorylase Kinase

AbstractBackground:PHKG2gene mutation can lead to liver phosphorylase kinase (PhK) deficiency, which is related to glycogen storage disease type IX (GSD IX). GSD IXc due toPHKG2mutation is the second most common GSD IX.Methods:We identified a novel mutation (c.553C>T, p.Arg185X) inPHKG2in a Chinese family and verified it by next-generation and Sanger sequencing. The mutation spectrum of thePHKG2gene was summarized based on 25 GSD IXc patients withPHKG2mutations.Results:We found that missense mutation (39%) was the most common type of mutation, followed by nonsense mutation (23%). Mutations were more prevalent in Asian (12/25) and European (9/25) populations than in populations from elsewhere. The exons had more sites of mutation than the introns, and exons 3 and 6 were the most frequent sites of mutations.Conclusions:This study expands our knowledge of thePHKG2gene mutation spectrum, providing a molecular basis for GSD IXc.

Spectrum of Ankyrin Mutations in Hereditary Spherocytosis: A Case Report and Review of the Literature

2018 ◽  
Vol 140 (2) ◽  
pp. 77-86 ◽  
Author(s):  
Yeping Luo ◽  
Zhuoying Li ◽  
Lihua Huang ◽  
Jing Tian ◽  
Menglong Xiong ◽  
...  
Keyword(s):  
Hereditary Spherocytosis ◽  
Novel Mutation ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Mutation Spectrum ◽  
Chinese Family ◽  
Review Of The Literature ◽  
Newborn Period ◽  
Gene Splicing ◽  
Generation Sequencing

Background/Aims: Hereditary spherocytosis (HS) is a common pediatric hemolytic anemia caused by congenital red blood cell defects. HS due to ankyrin 1 (ANK1) mutations is the most common type. We explored an ANK1 mutation from an HS patient and reviewed the literature. Methods: We detected the mutation in a Chinese family in which 2 members were diagnosed with HS by next-generation sequencing. The proband was diagnosed with HS in the newborn period, based on clinical manifestations, laboratory data, and family history. The mutation spectrum of the ANK1 gene was summarized based on 85 patients diagnosed with HS carrying ANK1 mutations, and the ANK1 mutation spectrum was summarized and analyzed. Results: We identified a novel mutation affecting ANK1 gene splicing (a splicing mutation) in both the patient and her mother, which is a substitution of T>G 2 nt after exon 25 in intron 26. The study expands our knowledge of the ANK1 gene mutation spectrum, providing a molecular basis for HS. Conclusion: A novel ANK1 mutation (NM_000037.3, c.2960+2T>G, intron 26) that is potentially associated with HS was identified. To date, 80 ANK1 mutations have been reported to be associated with HS in humans.

A novel variant in PAX6 as the cause of aniridia in a Chinese family

2020 ◽  
Author(s):  
Xin Jin ◽  
Wei Liu ◽  
HouBin Huang
Keyword(s):  
Nonsense Mutation ◽  
Novel Mutation ◽  
Causative Mutation ◽  
Chinese Family ◽  
The Novel ◽  
Targeted Next Generation Sequencing ◽  
Iris Defect ◽  
The Family ◽  
Novel Variant ◽  
Pax6 Mutation

Abstract Background: Aniridia is a kind of congenital human panocular anomaly, which is related to PAX6 commonly. Methods: A Chinese Aniridia pedigree underwent ophthalmic examinations, including visual acuity, slit lamp and fundoscopy examination. The targeted next-generation sequencing of Aniridia genes was used to identify the causative mutation. Results: A novel heterozygous PAX6 nonsense mutation c.619A>T (p.K207*) was identified in the Chinese autosomal dominant family with aniridia. Phenotypes related to the novel mutation include nystagmus, iris defect, cataract and absence of macular fovea. Conclusion: The novel nonsense mutation in PAX6 was responsible for aniridia phenotype in the family. which expands the spectrum of the PAX6 mutation and its associated phenotype.

scholarly journals Cochlear Implantation in a Patient with a Novel POU3F4 Mutation and Incomplete Partition Type-III Malformation

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xiuhua Chao ◽  
Yun Xiao ◽  
Fengguo Zhang ◽  
Jianfen Luo ◽  
Ruijie Wang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cochlear Implantation ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Bioinformatic Analysis ◽  
Chinese Family ◽  
Whole Exome ◽  
Novel Variant ◽  
Genetic Features ◽  
The Right

Aims. This study is aimed at (1) analyzing the clinical manifestations and genetic features of a novel POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family and (2) reporting the outcomes of cochlear implantation in a patient with this mutation. Methods. A patient who was diagnosed as the IP-III malformation underwent cochlear implantation in our hospital. The genetic analysis was conducted in his family, including the whole-exome sequencing combined with Sanger sequencing and bioinformatic analysis. Clinical features, preoperative auditory and speech performances, and postoperative outcomes of cochlear implant (CI) were assessed on the proband and his family. Results. A novel variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was detected in the family, which was cosegregated with the hearing loss. This variant was absent in 200 normal-hearing persons. The phylogenetic analysis and structure modeling of Pou3f4 protein further confirmed that the novel mutation was pathogenic. The proband underwent cochlear implantation on the right ear at four years old and gained greatly auditory and speech improvement. However, the benefits of the CI declined about three and a half years postoperation. Though the right ear had been reimplanted, the outcomes were still worse than before. Conclusion. A novel frame shift variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was identified in a Chinese family with X-linked inheritance hearing loss. A patient with this mutation and IP-III malformation could get good benefits from CI. However, the outcomes of the cochlear implantation might decline as the patient grows old.

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