scholarly journals New PTEN mutation identified in a patient with rare bilateral choroidal ganglioneuroma

2020 ◽  
Author(s):  
Zhaoxin Jiang ◽  
Ting Zhang ◽  
Chonglin Chen ◽  
Limei Sun ◽  
Songshan Li ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
De Novo ◽  
Family Members ◽  
Genetic Alterations ◽  
Unrelated Control ◽  
Pten Mutation ◽  
Whole Exome ◽  
The Family ◽  
Multiple Abnormalities ◽  
Human Genome Reference

Abstract Background: Choroidal ganglioneuroma is an extremely rare tumor, and there is little knowledge regarding its pathogenesis. We aimed to investigate the phenotypic and genetic alterations in one sporadic patient with a rare case of bilateral choroidal ganglioneuroma. Methods: A 6-year-old boy with histological diagnosis of bilateral ganglioneuroma was recruited for the study. Comprehensive ophthalmic examinations were performed. Genomic DNA was extracted from the peripheral blood samples collected from the patient, his unaffected family members, and 200 unrelated control subjects from the same population. Whole exome sequencing was performed and raw reads were aligned to the human genome reference (hg19) using Burrows-Wheeler Aligner. DNA from all available family members was Sanger sequenced for segregation analysis. Results: Extensive bilateral retinal detachments were observed via optical coherence tomography. Diffuse thickening of choroid was identified with ultrasound B scan and magnetic resonance imaging. Genetic analysis revealed the presence of a novel heterozygous PTEN frameshift mutation, c.498delA (p.Thr167LeufsTer16), in exon 6. It was present in the affected individual, but not in any of the family members. Genetic analysis revealed that there was no mutation in neurofibromatosis-related genes in the family. Upon performing comprehensive systemic examinations, no obvious abnormalities in other organs were observed. Conclusions: A novel de novo PTEN mutation was identified in a patient with bilateral choroidal ganglioneuroma. Although PTEN mutations are known to induce multiple abnormalities, choroidal ganglioneuroma can be the first manifestation without abnormalities in other organs. Further studies are needed to confirm the association between choroidal ganglioneuroma and PTEN mutation.

scholarly journals New mutation in PTEN identified in patient with rare bilateral choroidal ganglioneuroma

2020 ◽  
Author(s):  
Zhaoxin Jiang ◽  
Ting Zhang ◽  
Chonglin Chen ◽  
Limei Sun ◽  
Songshan Li ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
De Novo ◽  
Family Members ◽  
Genetic Alterations ◽  
Unrelated Control ◽  
Pten Mutation ◽  
Whole Exome ◽  
New Association ◽  
Multiple Abnormalities ◽  
Human Genome Reference

Abstract Background: Choroidal ganglioneuroma is an extremely rare tumor, with little known regarding its pathogenesis. The present study aimed to investigate the phenotype and genetic alterations in one sporadic patient with rare bilateral choroidal ganglioneuroma.Methods: A 6-year-old boy with histological diagnosis of bilateral ganglioneuroma was recruited in this study. Comprehensive ophthalmic examinations were performed in the patient. Genomic DNA was extracted from peripheral blood collected from the patient, the patient's unaffected family members, and from 200 unrelated control subjects from the same population. Whole exome sequencing was carried out and raw reads were aligned to the human genome reference (hg19) using the Burrows Wheeler Aligner. All available family members were subjected to Sanger sequencing for segregation analysis.Results: Bilateral and extensive retinal detachments were observed in OCT. The diffuse thickening of choroid was identified in B scan and MRI. Genetic analysis revealed the presence of a novel heterozygous PTEN frameshift mutation, c.498delA (p.Thr167LeufsTer16), in exon 6. It was identified in the affected individual, but not in any of the unaffected family members. Genetic analysis showed that there was no mutant in neurofibromatosis-related genes. There were no obvious abnormalities in other organs in comprehensive systemic examinations. Conclusions: A novel de novo PTEN mutation was identified in a bilateral choroidal ganglioneuroma case. Although PTEN mutation has been considered to induces multiple abnormalities, choroidal ganglioneuroma can be the first manifestation without abnormalities in other organs. Further studies are needed to confirm this new association between choroidal ganglioneuroma and the PTEN mutation.

scholarly journals New PTEN mutation identified in a patient with rare bilateral choroidal ganglioneuroma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhaoxin Jiang ◽  
Ting Zhang ◽  
Chonglin Chen ◽  
Limei Sun ◽  
Songshan Li ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Frameshift Mutation ◽  
De Novo ◽  
Family Members ◽  
Genetic Alterations ◽  
Unrelated Control ◽  
Whole Exome ◽  
The Family ◽  
Multiple Abnormalities ◽  
Human Genome Reference

Abstract Background Choroidal ganglioneuroma is an extremely rare tumor, and there is little knowledge regarding its pathogenesis. We aimed to investigate the phenotypic and genetic alterations in one sporadic patient with a rare case of bilateral choroidal ganglioneuroma. Methods A 6-year-old boy with histological diagnosis of bilateral ganglioneuroma was recruited for the study. Comprehensive ophthalmic examinations were performed. Genomic DNA was extracted from the peripheral blood samples collected from the patient, his unaffected family members, and 200 unrelated control subjects from the same population. Whole exome sequencing was performed and raw reads were aligned to the human genome reference (hg19) using Burrows-Wheeler Aligner. DNA from all available family members was Sanger sequenced for segregation analysis. Results Extensive bilateral retinal detachments were observed via optical coherence tomography. Diffuse thickening of choroid was identified with ultrasound B scan and magnetic resonance imaging. Genetic analysis revealed the presence of a novel heterozygous PTEN frameshift mutation, c.498delA (p.Thr167LeufsTer16), in exon 6. It was present in the affected individual, but not in any of the family members. Genetic analysis revealed that there was no mutation in neurofibromatosis-related genes in the family. Upon performing comprehensive systemic examinations, no obvious abnormalities in other organs were observed. Conclusions A novel de novo PTEN mutation was identified in a patient with bilateral choroidal ganglioneuroma. Although PTEN mutations are known to induce multiple abnormalities, choroidal ganglioneuroma can be the first manifestation without abnormalities in other organs. Further studies are needed to confirm the association between choroidal ganglioneuroma and PTEN mutation.

scholarly journals New mutation in PTEN identified in patient with rare bilateral choroidal ganglioneuroma

2020 ◽  
Author(s):  
Zhaoxin Jiang ◽  
Ting Zhang ◽  
Chonglin Chen ◽  
Limei Sun ◽  
Songshan Li ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
De Novo ◽  
Family Members ◽  
Genetic Alterations ◽  
Unrelated Control ◽  
Pten Mutation ◽  
Whole Exome ◽  
New Association ◽  
Multiple Abnormalities ◽  
Human Genome Reference

Abstract Background Choroidal ganglioneuroma is an extremely rare tumor, with little known regarding its pathogenesis. The present study aimed to investigate the phenotype and genetic alterations in one sporadic patient with rare bilateral choroidal ganglioneuroma. Methods A 6-year-old boy with histological diagnosis of bilateral ganglioneuroma was recruited in this study. Comprehensive ophthalmic examinations were performed in the patient. Genomic DNA was extracted from peripheral blood collected from the patient, the patient's unaffected family members, and from 200 unrelated control subjects from the same population. Whole exome sequencing was carried out and raw reads were aligned to the human genome reference (hg19) using the Burrows Wheeler Aligner. All available family members were subjected to Sanger sequencing for segregation analysis. Results Bilateral and extensive retinal detachments were observed in OCT. The diffuse thickening of choroid was identified in B scan and MRI. Genetic analysis revealed the presence of a novel heterozygous PTEN frameshift mutation, c.498delA (p.Thr167LeufsTer16), in exon 6. It was identified in the affected individual, but not in any of the unaffected family members. Genetic analysis showed that there was no mutant in neurofibromatosis-related genes. There were no obvious abnormalities in other organs in comprehensive systemic examinations. Conclusions A novel de novo PTEN mutation was identified in a bilateral choroidal ganglioneuroma case. Although PTEN mutation has been considered to induces multiple abnormalities, choroidal ganglioneuroma can be the first manifestation without abnormalities in other organs. Further studies are needed to confirm this new association between choroidal ganglioneuroma and the PTEN mutation.

scholarly journals New PTEN mutation identified in a patient with rare bilateral choroidal ganglioneuroma

2020 ◽  
Author(s):  
Zhaoxin Jiang ◽  
Ting Zhang ◽  
Chonglin Chen ◽  
Limei Sun ◽  
Songshan Li ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Frameshift Mutation ◽  
De Novo ◽  
Family Members ◽  
Genetic Alterations ◽  
Unrelated Control ◽  
Whole Exome ◽  
The Family ◽  
Multiple Abnormalities ◽  
Human Genome Reference

Abstract Background: Choroidal ganglioneuroma is an extremely rare tumor, and there is little knowledge regarding its pathogenesis. We aimed to investigate the phenotypic and genetic alterations in one sporadic patient with a rare case of bilateral choroidal ganglioneuroma.Methods: A 6-year-old boy with histological diagnosis of bilateral ganglioneuroma was recruited for the study. Comprehensive ophthalmic examinations were performed. Genomic DNA was extracted from the peripheral blood samples collected from the patient, his unaffected family members, and 200 unrelated control subjects from the same population. Whole exome sequencing was performed and raw reads were aligned to the human genome reference (hg19) using Burrows-Wheeler Aligner. DNA from all available family members was Sanger sequenced for segregation analysis.Results: Extensive bilateral retinal detachments were observed via optical coherence tomography. Diffuse thickening of choroid was identified with ultrasound B scan and magnetic resonance imaging. Genetic analysis revealed the presence of a novel heterozygous PTEN frameshift mutation, c.498delA (p.Thr167LeufsTer16), in exon 6. It was present in the affected individual, but not in any of the family members. Genetic analysis revealed that there was no mutation in neurofibromatosis-related genes in the family. Upon performing comprehensive systemic examinations, no obvious abnormalities in other organs were observed.Conclusions: A novel de novo PTEN mutation was identified in a patient with bilateral choroidal ganglioneuroma. Although PTEN mutations are known to induce multiple abnormalities, choroidal ganglioneuroma can be the first manifestation without abnormalities in other organs. Further studies are needed to confirm the association between choroidal ganglioneuroma and PTEN mutation.

scholarly journals Genotypes and Phenotypes of MEF2C Haploinsufficiency Syndrome: New Cases and Novel Point Mutations

2021 ◽  
Vol 9 ◽  
Author(s):  
Lin Wan ◽  
Xinting Liu ◽  
Linyan Hu ◽  
Huimin Chen ◽  
Yulin Sun ◽  
...  
Keyword(s):  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Point Mutations ◽  
Clinical Manifestations ◽  
Poor Performance ◽  
Genetic Alterations ◽  
Mendelian Inheritance ◽  
Whole Exome ◽  
Patients With Epilepsy ◽  
Free Status

Aim: MEF2C haploinsufficiency syndrome (MCHS) is a severe neurodevelopmental disorder. We describe the clinical phenotypes and genotypes of seven patients with MCHS to enhance the understanding of clinical manifestations and genetic alterations associated with MCHS.Method: Seven patients (6 females and 1 male, aged between 2 years 5 months and 6 years) who had MEF2C mutations, and their parents underwent trio-based whole-exome sequencing; subsequently, their clinical features were assessed. A literature review of patients with MCHS was performed by searching the PubMed and Online Mendelian Inheritance in Man databases.Results: Seven mutations were identified, of which six were unreported in the past; of the reported cases, five patients had de novo mutations but two had an undefined inheritance pattern. All patients presented delays in developmental milestones, severe intellectual disabilities and lack of speech. Six patients exhibited infantile hypotonia, five patients experienced stereotypic movements and were unable to walk, four patients exhibited poor eye contact indicative of autism and two showed poor performance. While six patients experienced seizure, five among them became seizure free after receiving anti-seizure medicine. Three patients showed a regression in their development, whereas the mothers of two patients exhibited mosaicism but were healthy without any abovementioned symptoms.Interpretation: Regression was not a common phenomenon but occurred in MCHS. The prognosis of MCHS patients with epilepsy was good, but most patients can achieve a seizure-free status. Healthy people may have low-level mosaicism and carry a pathogenic MEF2C mutation.

scholarly journals Identification of the FirstDe Novo UBIAD1Gene Mutation Associated with Schnyder Corneal Dystrophy

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Benjamin R. Lin ◽  
Ricardo F. Frausto ◽  
Rosalind C. Vo ◽  
Stephan Y. Chiu ◽  
Judy L. Chen ◽  
...  
Keyword(s):  
Family History ◽  
Missense Mutation ◽  
Protein Function ◽  
De Novo ◽  
Family Members ◽  
Corneal Dystrophy ◽  
Slit Lamp ◽  
Slit Lamp Examination ◽  
The Family ◽  
Schnyder Corneal Dystrophy

Purpose.To report the identification of the firstde novo UBIAD1missense mutation in an individual with Schnyder corneal dystrophy (SCD).Methods.A slit lamp examination was performed on a 47-year-old woman without a family history of corneal disorders. The proband’s parents, two sisters, and son were also examined and genomic DNA from all six individuals was collected. The exons and exon-intron boundaries ofUBIAD1were screened using Sanger sequencing. Identified mutations were screened for in 200 control chromosomes.In silicoanalysis predicted the impact of identified mutations on protein function and structure.Results.Slit lamp examination of the proband revealed findings consistent with SCD. Corneas of the family members appeared unaffected. Screening ofUBIAD1in the proband identified a novel heterozygous c.308C>T mutation, predicted to encode the missense amino acid substitution p.(Thr103Ile). This mutation was not identified in any of the family members or in 200 control chromosomes and was predicted to be damaging to normal protein function and structure.Conclusions.We present a novel heterozygousde novomissense mutation inUBIAD1, p.(Thr103Ile), identified in a patient with classic clinical features of SCD. This highlights the value of genetic testing in clinical diagnostic settings, even in the absence of a positive family history.

scholarly journals Osteogenesis Imperfecta With Cerebral Atherosclerosis: A Family Report

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A209-A209
Author(s):  
Junyu He ◽  
Zhihong Liao
Keyword(s):  
Osteogenesis Imperfecta ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Manifestation ◽  
Family Members ◽  
Whole Exome ◽  
The Family ◽  
Col1a2 Gene ◽  
History Of ◽  
Severe Fracture

Abstract Background: Osteogenesis imperfecta (OI) is a rare hereditary connective tissue disease. It is mainly associated with pathogenic variants in COL1A1 or COL1A2. Patients with OI usually have repeated history of bone fractures. Besides, osteogenesis imperfecta is associated with some cardiovascular complications, such as aortic and mitral valve dysfunction, aneurysm and aortic dissection. But the relationship between these diseases has not been well studied. Case Presentation: A 55-year-old man was admitted to our hospital mainly due to “dizziness for 2 hours”. He had a 4-month history of hypertension and a history of smoking for more than 20 years. He had no history of drinking alcohol. He had hunchback and O-type legs. Besides, the patient and some of his relatives had a history of repeated brittle fractures,which was considered as “osteogenesis imperfecta”. The clinical manifestation of OI in this family varies to a certain extent, from simple tooth disintegration to severe fracture deformity. The most serious patient of his family was unable to walk. CT and MRI revealed multiple systemic arteriosclerosis, including vertebral artery, posterior inferior cerebellar artery, cervical artery, and bilateral cerebellar multiple lacunar cerebral infarction. The blood sample of the patient was tested by whole exome sequencing, and the saliva samples of the patient’s family members were tested by Sanger sequencing. A mutation c.3159 + 2T > A was detected in COL1A2 gene associated with OI, also found in the other affected family members, which had not been reported before. It was a segregating mutation in the family. The clinical severity of the family members was heterogeneous. Discussion: This case is worth learning from the following aspects: 1. A pathogenic heterozygous mutation, c.3159 + 2T > A was detected in COL1A2 gene in the patient with OI, which is not reported in previous cases of OI. 2. The clinical manifestation of OI in this family varies to a certain extent, from simple tooth disintegration to severe fracture deformity. The most serious patient of his family was unable to walk. It presented the clinical heterogeneity of OI. Further basic researh on the mutation site of related gene of OI are needed. 3. We found the possibility of developing cerebral atherosclerosis in patients with OI. Therefore, patients with OI should give up smooking, exercise properly and keep on a low fat diet. They should pay attention to control blood pressure and blood lipid so as to reduce the risk of atherosclerosis. Conclusion: A c.3159 + 2T>A mutation in COL1A2 gene detected by whole exome sequencing was the causing reason of OI, the discovery enriched the gene mutation spectrum of OI. We also found that OI may have relationship with premature atherosclerosis, and the abnormal bones of the cervical spine may lead to vertebrobasilar ischemia.

scholarly journals A Chinese Patient with Spastic Paraplegia Type 4 with a De Novo Mutation in the SPAST Gene

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Li Xu ◽  
Zijuan Peng ◽  
Chunhui Zhou ◽  
Jiqing Wang ◽  
Hunjin Luo ◽  
...  
Keyword(s):  
Missense Mutation ◽  
De Novo ◽  
Chinese Patient ◽  
Chinese Woman ◽  
De Novo Mutation ◽  
Spastic Paraplegia ◽  
Gene Segregation ◽  
Whole Exome ◽  
The Family ◽  
Family Gene

Background. Spastic paraplegia type 4 (SPG4) is the most common type of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. Case Presentation. We report the case of a 27-year-old pregnant Chinese woman with HSP in whom we identified a missense mutation in the SPAST gene (c.1496G>A, p.Arg499His) and a nonsense mutation in the NEFH gene (c.289G>T, p.Glu97 ∗ ) via whole-exome sequencing; this finding corroborated that of Sanger sequencing. The patient exhibited the pure SPG4 phenotype with onset during childhood. The SPAST mutation was absent in the parents and paternal relatives. However, the NEFH mutation was identified in five people with no clinical phenotype. Based on theoretical conjecture and the family gene segregation information, we concluded that the SPAST mutation, but not the NEFH mutation, accounted for the proband’s phenotype. Eventually, the woman gave birth to a healthy baby girl with the NEFH mutation. Conclusion. In this report, we identified a missense mutation in the SPAST gene (p.Arg499His) in a 27-year-old pregnant Chinese woman with HSP. We believe that this study expands the knowledge about the clinical parameters and mutation spectrum of SPG4.

P0065DOUBLE MUTATION INHERITANCE IN PATIENTS WITH FOCAL SEGMENTAL GLOMERULOSCLEROSIS AND ALPORT SUNDROME

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jingyuan Xie
Keyword(s):  
Genetic Analysis ◽  
Focal Segmental Glomerulosclerosis ◽  
Clinical Symptoms ◽  
Compound Heterozygous ◽  
Incomplete Penetrance ◽  
Digenic Inheritance ◽  
Segmental Glomerulosclerosis ◽  
Whole Exome ◽  
The Family ◽  
Genetic Pools

Abstract Background and Aims Focal segmental glomerulosclerosis (FSGS) and Alport syndrome (AS) are the leading causes of ESRD globally. FSGS and AS are clinically heterogeneous nephropathies and mainly genetic causes are the mutations in genes expressed in podocytes and glomerular basement membrane (GBM) respectively. A simple Mendelian model fail to explain the genetic control of both nephropathies completely because of the heterogeneous nature and presence of incomplete penetrance. Therefore, here we investigated the possible digenic control of FSGS and AS. Method To detect the double mutational (mono- or di-genic) cause of FSGS and AS, we conducted whole exome sequencing (WES) and panel sequencing in 67 kidney patients during the period of four years (2015 to June 2019). Inclusion criteria was the proband's clinical symptoms confirming the FSGS or AS based on clinical symptoms and renal biopsy. Clinical and genetic analyses were implemented to correlate the phenotypes with genotypes. Results Genetic analysis discovered that 35 out of 67 (52.23%) had genetic cause of selected nephropathies and 24 out of 35 (68.57%) had mutations in COL4A (3,4 & 5) genes and 11 (31.42%) in other genes. Interestingly, we found 7 out of 35 patients (20%) with double mutations (mono- or di-genic) in COL4A3/COL4A4 genes. After the mentioned period, during routine genetic screening, we also found another patient having double mutations in COL4A3 gene. Subsequently, Sanger sequencing confirmed that the identified mutations were co-segregating with the disease(s) in an incomplete penetrance fashion within the family. Lastly, we found 16 mutations in 8 patients having either monogenic or digeneic double mutations in COL4A3 and/or COL4A4 genes. In sum, we found 12 (75%) mutations in COL4A3 and 4 in COL4A4 (25%), and5 probands (62.5%) had compound heterozygous mutations in COL4A3, 1 proband (12.5%) had in COL4A4 and 2 probands (25%) had digenic (COL4A3/COL4A4) mutations. Last of all, among all the mutations, 10 were novel and 6 have been described previously. Conclusion This genetic analysis provides the first evidence for digenic inheritance of FSGS. The nephrologists and clinical geneticists should keep this possibility in mind for the accuracy in diagnosis, disease management and genetic counseling in future. Additionally, we are also adding 10 novel mutations in COL4A3 and COL4A4 genetic pools.

scholarly journals Analysis of the Genetic Characteristics of a Chinese Family With Otosclerosis

2020 ◽  
pp. 014556132091062
Author(s):  
Yongli Zhang ◽  
Qi Tang ◽  
Ruoyan Xue ◽  
Xiaohui Zhu ◽  
Hua Yang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Autosomal Dominant ◽  
Family Members ◽  
Autosomal Dominant Inheritance ◽  
Dominant Inheritance ◽  
Genetic Characteristics ◽  
Whole Exome ◽  
The Family

Background: Otosclerosis is a focal lesion of the inner ear. The role of genetic factors in the pathogenesis of otosclerosis has received increasing attention. We analyzed the clinical manifestations, inheritance pattern, and pathogenic genes in a family with otosclerosis. Methods: We collected clinical data and generated a family pedigree. High-throughput second-generation sequencing technology was used to identify candidate genes by performing whole-exome sequencing of 7 members of the family, and Sanger sequencing was performed to validate candidate gene mutations in the 7 family members. Results: Otosclerosis was characterized by autosomal dominant inheritance in this family. Whole-exome sequencing did not reveal mutation sites in known deafness-related genes. However, a c.2209A > G (p.T737A) mutation was detected in exon 6 of the SP1 gene, which is associated with the COL1A1 gene. This mutation was a pathogenic mutation, and Sanger sequencing confirmed that this mutation cosegregated with the clinical phenotype among the family members. Conclusions: The pattern of otosclerosis in this family is consistent with autosomal dominant inheritance, and the SP1 gene, harboring the c.2209A > G (p.T737A) mutation in exon 6, may be the causative gene of otosclerosis in this family.

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