scholarly journals Identification of Novel Mutations inABCA4Gene: Clinical and Genetic Analysis of Indian Patients with Stargardt Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Rajani Battu ◽  
Anshuman Verma ◽  
Ramesh Hariharan ◽  
Shuba Krishna ◽  
Ravi Kiran ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Vision Loss ◽  
Variant Calling ◽  
Signs And Symptoms ◽  
Cost Effective ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Stargardt Disease ◽  
Indian Patients ◽  
Targeted Gene Sequencing

Stargardt disease (STGD) is the leading cause of juvenile macular degeneration associated with progressive central vision loss, photophobia, and colour vision abnormalities. In this study, we have described the clinical and genetic features of Stargardt patients from an Indian cohort. The next generation sequencing was carried out in five clinically confirmed unrelated patients and their family members using a gene panel comprising 184 retinal specific genes. Sequencing results were analyzed by read mapping and variant calling in genes of interest, followed by their verification and interpretation. Genetic analysis revealedABCA4mutations in all of the five unrelated patients. Among these, four patients were found with compound heterozygous mutations and another one had homozygous mutation. All the affected individuals showed signs and symptoms consistent with the disease phenotype. We report two novelABCA4mutations in Indian patients with STGD disease, which expands the existing spectrum of disease-causing variants and the understanding of phenotypic and genotypic correlations. Screening for causative mutations in patients with STGD using panel of targeted gene sequencing by NGS would be a cost effective tool, might be helpful in confirming the precise diagnosis, and contributes towards the genetic counselling of asymptomatic carriers and isolated patients.

Clinical and molecular genetic characterization of two patients with mutations in the phosphoglucomutase 1 (PGM1) gene

2018 ◽  
Vol 31 (7) ◽  
pp. 781-788 ◽  
Author(s):  
Yu Ding ◽  
Niu Li ◽  
Gouying Chang ◽  
Juan Li ◽  
Ruen Yao ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Chinese Han ◽  
Targeted Gene Sequencing ◽  
Molecular Genetic Characterization

Abstract Background The phosphoglucomutase 1 (PGM1) enzyme plays a central role in glucose homeostasis by catalyzing the inter-conversion of glucose 1-phosphate and glucose 6-phosphate. Recently, PGM1 deficiency has been recognized as a cause of the congenital disorders of glycosylation (CDGs). Methods Two Chinese Han pediatric patients with recurrent hypoglycemia, hepatopathy and growth retardation are described in this study. Targeted gene sequencing (TGS) was performed to screen for causal genetic variants in the genome of the patients and their parents to determine the genetic basis of the phenotype. Results DNA sequencing identified three variations of the PGM1 gene (NM_002633.2). Patient 1 had a novel homozygous mutation (c.119delT, p.Ile40Thrfs*28). In patient 2, we found a compound heterozygous mutation of c.1172G>T(p.Gly391Val) (novel) and c.1507C>T(p.Arg503*) (known pathogenic). Conclusions This report deepens our understanding of the clinical features of PGM1 mutation. The early molecular genetic analysis and multisystem assessment were here found to be essential to the diagnosis of PGM1-CDG and the provision of timely and proper treatment.

scholarly journals Accurate interpretation of genetic variants in sudden unexpected death in infancy by trio-targeted gene-sequencing panel analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Keita Shingu ◽  
Takehiko Murase ◽  
Takuma Yamamoto ◽  
Yuki Abe ◽  
Yoriko Shinba ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Cause Of Death ◽  
Genetic Variants ◽  
De Novo ◽  
Sudden Unexpected Death ◽  
Compound Heterozygous ◽  
Unexpected Death ◽  
Accurate Interpretation ◽  
Clinically Significant ◽  
Targeted Gene Sequencing

AbstractIn sudden unexpected death in infancy cases, postmortem genetic analysis with next-generation sequencing potentially can extract candidate genes associated with sudden death. However, it is difficult to accurately interpret the clinically significant genetic variants. The study aim was to conduct trio analysis of cases of sudden unexpected death in infancy and their parents to more accurately interpret the clinically significant disease-associated gene variants associated with cause of death. From the TruSight One panel targeting 4813 genes we extracted candidate genetic variants of 66 arrhythmia-, 63 inherited metabolic disease-, 81 mitochondrial disease-, and 6 salt-losing tubulopathy-related genes in 7 cases and determined if they were de novo or parental-derived variants. Thirty-four parental-derived variants and no de novo variants were found, but none appeared to be related to the cause of death. Using trio analysis and an in silico algorithm to analyze all 4813 genes, we identified OBSCN of compound heterozygous and HCCS of hemizygous variants as new candidate genetic variants related to cause of death. Genetic analysis of these deceased infants and their living parents can provide more accurate interpretation of the clinically significant genetic variants than previously possible and help confirm the cause of death.

scholarly journals Genetic, structural and clinical analysis of spastic paraplegia 4

2021 ◽  
Author(s):  
Parizad Varghaei ◽  
Mehrdad A Estiar ◽  
Setareh Ashtiani ◽  
Simon Veyron ◽  
Kheireddin Mufti ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
De Novo ◽  
Clinical Manifestations ◽  
Signs And Symptoms ◽  
Clinical Analysis ◽  
Copy Number Variations ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Spastic Paraplegia ◽  
Synonymous Mutations

Background: Spastic paraplegia type 4 (SPG4), resulting from heterozygous mutations in the SPAST gene, is the most common form among the heterogeneous group of hereditary spastic paraplegias (HSPs). Objective: To study genetic and clinical characteristics of SPG4 across Canada. Methods: The SPAST gene was analyzed in a total of 696 HSP patients from 431 families by either HSP-gene panel sequencing or whole exome sequencing (WES). We used Multiplex ligation-dependent probe amplification to analyze copy number variations (CNVs), and performed in silico structural analysis of selected mutations. Clinical characteristics of patients were assessed, and long-term follow-up was done to study genotype-phenotype correlations. Results: We identified 157 SPG4 patients from 65 families who carried 41 different SPAST mutations, six of which are novel and six are CNVs. We report novel aspects of mutations occurring in Arg499, a case with homozygous mutation, a family with probable compound heterozygous mutations, three patients with de novo mutations, three cases with pathogenic synonymous mutation, co-occurrence of SPG4 and multiple sclerosis, and novel or rarely reported signs and symptoms seen in SPG4 patients. Conclusion: Our study demonstrates that SPG4 is a heterogeneous type of HSP, with diverse genetic features and clinical manifestations. In rare cases, biallelic inheritance, de novo mutation, pathogenic synonymous mutations and CNVs should be considered.

Clinical, biochemical and genotypical characteristics in biotinidase deficiency

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Abdurrahman Akgun ◽  
Askin Sen ◽  
Hasan Onal
Keyword(s):  
Autosomal Recessive ◽  
Vision Loss ◽  
Study Data ◽  
Biotinidase Deficiency ◽  
Enzyme Deficiency ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
The Central Nervous System

Abstract Objectives Hypotonia, lethargy, eczema, alopecia, conjunctivitis, ataxia, hearing loss, optic atrophy, cognitive retardation, and seizures can occur in patients with biotinidase deficiency, and it is inherited as autosomal recessive. The aim of this study was to evaluate the cases followed up with the diagnosis of biotinidase deficiency in our unit, in terms of clinical, biochemical and genetic analyses. Methods A total of 112 cases followed up in our centre with the diagnosis of biotinidase deficiency between August 2018–September 2020 were included in the study. Data were collected retrospectively. Results A total of 112 cases (55.4% male, mean age: 2.2 ± 2.8 years) diagnosed with biotinidase deficiency were evaluated. Diagnoses were made by newborn screening in 90.2% of the cases, by family screening in 4.5%, and by investigating symptoms in 5.4%. The most frequently (27.5%) detected mutations were c.1330G>C (p.D444H)/c.1330G>C (p.D444H) homozygous mutation, followed by (13.0%) c.1330G>C (p.D444H)/c.470G>A (p.R157H) compound heterozygous mutation, and (13.0%) c.470G>A (p.R157H)/c.470G>A (p.R157H) homozygous mutation. Biotinidase enzyme levels were found to be higher in patients with the p.D444H homozygous mutation than patients with other mutations. Biotin treatment was started in all patients with enzyme deficiency. Conclusions Since the treatment is inexpensive and easily available, it is vital to detect this disease before symptom onset, especially findings related to the central nervous system, hearing and vision loss. In patients diagnosed with enzyme deficiency, the diagnosis should be definitively confirmed by genetic analysis.

scholarly journals A Mild Phenotype Caused by Two Novel Compound Heterozygous Mutations in CEP290

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1240
Author(s):  
Agnieszka Rafalska ◽  
Anna M. Tracewska ◽  
Anna Turno-Kręcicka ◽  
Milena J. Szafraniec ◽  
Marta Misiuk-Hojło
Keyword(s):  
Vision Loss ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Mild Phenotype ◽  
Cone Function ◽  
Retinal Disorders ◽  
Molecular Inversion Probes ◽  
Disease Experience ◽  
The Individual ◽  
Inherited Retinal Disorders

CEP290 is a ciliary gene frequently mutated in ciliopathies, resulting in a broad range of phenotypes, ranging from isolated inherited retinal disorders (IRDs) to severe or lethal syndromes with multisystemic involvement. Patients with non-syndromic CEP290-linked disease experience profound and early vision loss due to cone-rod dystrophy, as in Leber congenital amaurosis. In this case report, we describe two novel loss-of-function heterozygous alterations in the CEP290 gene, discovered in a patient suffering from retinitis pigmentosa using massive parallel sequencing of a molecular inversion probes library constructed for 108 genes involved in IRDs. A milder phenotype than expected was found in the individual, which serves to prove that some CEP290-associated disorders may display preserved cone function.

scholarly journals Predictive Value of Alvarado Score and Ultrasound in the Diagnosis of Acute Appendicitis (A prospective study

2021 ◽  
Vol 62 (4) ◽  
pp. 99-103
Author(s):  
Waleed Saadi Ahmed ◽  
Salah M. Tajer ◽  
Hend M. Sayaly
Keyword(s):  
Abdominal Pain ◽  
Acute Appendicitis ◽  
Signs And Symptoms ◽  
Cost Effective ◽  
General Surgeon ◽  
Emergency Ward ◽  
Alvarado Score ◽  
Combined Application ◽  
Abdominal Emergencies ◽  
A Prospective Study

Background:  Acute appendicitis is the commonest non traumatic cause of acute abdominal pain that needs surgical management .Alvarado score and ultrasonographies are the most cost effective, easy and available aids for diagnosis. The aim of the study was determining   the reliability of Alvarado score and ultrasound in the diagnosis of acute appendicitis. Results: The study was applied with 100 cases with different types of abdominal pain at presentation with 51 males and 49 females .The sensitivity was97.3% ,specificity 90%, and accuracy  89 of combined usage of Alvarado score and U/S findings preoperatively. Patients and method:  A prospective non-interventional study including patients admitted with suggestive history with signs and symptoms of acute appendicitis to the surgical emergency ward of Baghdad teaching hospital from July 1st 2017 to Feb 10th 2018, Alvarado score calculated and ultrasonography done for each patient enrolled in this study, then to be followed for intraoperative findings. Conclusions: Combined application of Alvarado score and U/S has sensitivity 94.1% ,specificity 90% and accuracy 89% . In our medical facility and emergency ward, acute appendicitis remains as one of the top acute abdominal emergencies needing surgery in patients presenting with atypical clinical finding. So diagnosis becomes difficult. So Alvarado score along with ultrasound findings are useful for increasing the reliability in emergency department for  accurate diagnosis of acute appendicitis therefore there should be training for the use of U/S by emergency physician and general surgeon in the diagnosis of acute appendicitis in order to decrease the rate of negative appendectomies .  

scholarly journals EFFECT OF PERINEAL REPAIR AND MUSHAKADI TAILA MATRABASTI IN MANAGEMENT OF RECTAL PROLAPSE (GUDABHARMSA): A CASE STUDY

2020 ◽  
Vol 8 (8) ◽  
pp. 4267-4270
Author(s):  
Sapna Maheshwari ◽  
Harshit Shah ◽  
Pragnesh Patel
Keyword(s):  
Rectal Prolapse ◽  
Signs And Symptoms ◽  
Cost Effective ◽  
Complete Rectal Prolapse ◽  
Full Thickness ◽  
Perineal Repair ◽  
Chief Complaints ◽  
Surgical Options ◽  
External Rectal Prolapse

Rectal prolapse can present in a variety of forms and is associated with a range of symptoms including pain, incomplete evacuation, bloody and/or mucous rectal discharge, and fecal incontinence or constipa-tion. Complete external rectal prolapse is characterized by a circumferential, full-thickness protrusion of the rectum through the anus, which may be intermittent or may be incarcerated and poses a risk of strangu-lation. There are multiple surgical options to treat rectal prolapse, and thus care should be taken to under-stand each patient’s symptoms, bowel habits, anatomy, and pre-operative expectations. We propose an al-gorithm based on available outcomes data in the literature, an understanding of ano-rectal physiology, and expert opinion that can serve as a guide to determining the rectal prolapse operation that will achieve the best possible postoperative outcomes for individual patients. Mushakadi Taila Matrabasti will be given in Sushrut Samhita as a treatment1 with perineal repair. So, it is really needed to find a safe, easier, less com-plicating, cost effective and fruitful approach for the management of disease through Ayurveda. A 62year old male patient came to the hospital with chief complaints of protrusion of mass from the anus with mu-cous discharge, constipation since last 5 years. He was diagnosed as complete rectal prolapse. Considering the signs and symptoms of rectal prolapse, the treatment of rectal prolapsed was planned with perineal re-pair and Mushakadi Taila Matarabasti as per mentioned in the treatment of Gudabhransha by Aacharya Sushruta.

STUDY OF ABSOLUTE, IMMATURE NEUTROPHIL COUNT AND CRP AS DIAGNOSTIC MARKERS FOR EARLY ONSET NEONATAL SEPSIS.

2021 ◽  
pp. 25-26
Author(s):  
Pooja Poswal ◽  
Manisha Rohilla ◽  
Sunil Arora ◽  
Irbinder Kour Bali
Keyword(s):  
Blood Culture ◽  
Neutrophil Count ◽  
Neonatal Sepsis ◽  
Hematological Parameters ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Cost Effective ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Clinical Signs And Symptoms

Introduction: Neonatal Sepsis is difcult to differentiate from other conditions due to non- specic clinical signs and symptoms. Inammation in neonates shows variations in hematological parameters. Our study is to evaluate the hematological parameters and C-reactive protein estimation in neonatal sepsis for early diagnosis. Material And Methods: It was a cross-sectional study including 80 neonates admitted in the neonatal care unit, 40 (proven sepsis) and 40 probable cases); blood culture being the gold standard. Hematological parameters, immature to total neutrophil ratio (I/T ratio), Absolute neutrophil count (ANC), CRP and Blood culture were done as per standard protocols. Results: ANC had highest sensitivity of 90% followed by I/T ratio (87.5%) and CRP (77.5%). The sensitivity and specicity for the combination of ANC and I/T ratio was 78.3% and 83.6% respectively. Conclusion: ANC, I/T Ratio and CRP are quick, simple and cost-effective routine laboratory tests which help in neonatal sepsis prediction and to start proper and timely antibiotic therapy.

scholarly journals COX deficiency and leukoencephalopathy due to a novel homozygous APOPT1/COA8 mutation

2020 ◽  
Vol 6 (4) ◽  
pp. e464 ◽  
Author(s):  
Carola Hedberg-Oldfors ◽  
Niklas Darin ◽  
Christer Thomsen ◽  
Christopher Lindberg ◽  
Anders Oldfors
Keyword(s):  
Genetic Analysis ◽  
Nonsense Mutation ◽  
Clinical Investigation ◽  
Brain Mri ◽  
Homozygous Mutation ◽  
Term Outcome ◽  
Complex Iv ◽  
Long Term Outcome ◽  
Long Term Follow Up

ObjectiveTo describe the long-term follow-up and pathogenesis in a child with leukoencephalopathy and cytochrome c oxidase (COX) deficiency due to a novel homozygous nonsense mutation in APOPT1/COA8.MethodsThe patient was clinically investigated at 3, 5, 9, and 25 years of age. Brain MRI, repeat muscle biopsies with biochemical, morphologic, and protein expression analyses were performed, and whole-genome sequencing was used for genetic analysis.ResultsClinical investigation revealed dysarthria, dysphagia, and muscle weakness following pneumonia at age 3 years. There was clinical regression leading to severe loss of ambulation, speech, swallowing, hearing, and vision. The clinical course stabilized after 2.5 years and improved over time. The MRI pattern in the patient demonstrated cavitating leukoencephalopathy, and muscle mitochondrial investigations showed COX deficiency with loss of complex IV subunits and ultrastructural abnormalities. Genetic analysis revealed a novel homozygous mutation in the APOPT1/COA8 gene, c.310T>C; p.(Gln104*).ConclusionsWe describe a novel nonsense mutation in APOPT1/COA8 and provide additional experimental evidence for a COX assembly defect in human muscle causing the complex IV deficiency. The long-term outcome of the disease seems in general to be favorable, and the characteristic MRI pattern with cavitating leukoencephalopathy in combination with COX deficiency should prompt for testing of the APOPT1/COA8 gene.

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