scholarly journals CAPN1 Variants as Cause of Hereditary Spastic Paraplegia Type 76

2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
Jesus Eduardo Garcia-Berlanga ◽  
Mariana Moscovich ◽  
Isaac Jair Palacios ◽  
Alejandro Banegas-Lagos ◽  
Augusto Rojas-Martinez ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Brain Mri ◽  
Young Female ◽  
Sequencing Analysis ◽  
Spastic Paraplegia ◽  
Case Presentation ◽  
Significant Family History ◽  
Hereditary Spastic Paraplegias ◽  
Whole Exome ◽  
Oculomotor Abnormalities

Background. Autosomal recessive hereditary spastic paraplegias (HSP) are a rare group of hereditary neurodegenerative disorders characterized by spasticity with or without other symptoms. SPG11 gene is the most common cause of autosomal recessive HSP. We report a case of autosomal recessive spastic paraplegia type 76 due to heterozygous variants of CAPN1 in an Argentinean subject. Case Presentation. A 38-year-old Argentinean female presented with progressive gait problems and instability of 15-year duration. Oculomotor abnormalities, ataxia, bradykinesia, cervical dystonia, and lower limb pyramidal signs were observed. Brain MRI was unremarkable. Whole-exome sequencing analysis identified two heterozygous variants in CAPN1. Conclusions. Clinicians should screen for CAPN1 mutation in a young female patient without significant family history with a spastic paraplegia syndrome associated with other symptoms.

Kindler's Syndrome with Recurrent Neutropenia: Report of Two Cases from Saudi Arabia

2020 ◽  
Author(s):  
Yousef Binamer ◽  
Muzamil A. Chisti
Keyword(s):  
Autosomal Recessive ◽  
Common Mechanism ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Skin Atrophy ◽  
Whole Exome ◽  
Infancy And Childhood ◽  
Genetics And Genomics ◽  
New Feature ◽  
Generation Sequencing

AbstractKindler syndrome (KS) is a rare photosensitivity disorder with autosomal recessive mode of inheritance. It is characterized by acral blistering in infancy and childhood, progressive poikiloderma, skin atrophy, abnormal photosensitivity, and gingival fragility. Besides these major features, many minor presentations have also been reported in the literature. We are reporting two cases with atypical features of the syndrome and a new feature of recurrent neutropenia. Whole exome sequencing analysis was done using next-generation sequencing which detected a homozygous loss-of-function (LOF) variant of FERMT1 in both patients. The variant is classified as a pathogenic variant as per the American College of Medical Genetics and Genomics guidelines. Homozygous LOF variants of FERMT1 are a common mechanism of KS and as such confirm the diagnosis of KS in our patients even though the presentation was atypical.

scholarly journals Challenges and Controversies in the Genetic Diagnosis of Hereditary Spastic Paraplegia

2021 ◽  
Vol 21 (4) ◽  
Author(s):  
Lydia Saputra ◽  
Kishore Raj Kumar
Keyword(s):  
Genetic Diagnosis ◽  
Spastic Paraplegia ◽  
Limb Weakness ◽  
Hereditary Spastic Paraplegias ◽  
Gene Testing ◽  
Testing Strategies ◽  
Whole Exome ◽  
The Right ◽  
Gene Panels ◽  
High Degree

Abstract Purpose of Review The hereditary spastic paraplegias (HSPs) are a group of disorders characterised by progressive lower limb weakness and spasticity. We address the challenges and controversies involved in the genetic diagnosis of HSP. Recent Findings There is a large and rapidly expanding list of genes implicated in HSP, making it difficult to keep gene testing panels updated. There is also a high degree of phenotypic overlap between HSP and other disorders, leading to problems in choosing the right panel to analyse. We discuss genetic testing strategies for overcoming these diagnostic hurdles, including the use of targeted sequencing gene panels, whole-exome sequencing and whole-genome sequencing. Personalised treatments for HSP are on the horizon, and a genetic diagnosis may hold the key to access these treatments. Summary Developing strategies to overcome the challenges and controversies in HSP may hold the key to a rapid and accurate genetic diagnosis.

scholarly journals Homozygous missense variant in the TTN gene causing autosomal recessive limb-girdle muscular dystrophy type 10

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Amjad Khan ◽  
Rongrong Wang ◽  
Shirui Han ◽  
Muhammad Umair ◽  
Safdar Abbas ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Recessive ◽  
Missense Variant ◽  
Pathogenic Variant ◽  
Limb Girdle Muscular Dystrophy ◽  
Molecular Diagnostic ◽  
Sequencing Analysis ◽  
Whole Exome

Abstract Background Limb-girdle muscular dystrophies (LGMDs) are large group of heterogeneous genetic diseases, having a hallmark feature of muscle weakness. Pathogenic mutations in the gene encoding the giant skeletal muscle protein titin (TTN) are associated with several muscle disorders, including cardiomyopathy, recessive congenital myopathies and limb-girdle muscular dystrophy (LGMD) type10. The phenotypic spectrum of titinopathies is expanding, as next generation sequencing (NGS) technology makes screening of this large gene possible. Aim This study aimed to identify the pathogenic variant in a consanguineous Pakistani family with autosomal recessive LGMD type 10. Methods DNA from peripheral blood samples were obtained, whole exome sequencing (WES) was performed and several molecular and bioinformatics analysis were conducted to identify the pathogenic variant. TTN coding and near coding regions were further amplified using PCR and sequenced via Sanger sequencing. Results Whole exome sequencing analysis revealed a novel homozygous missense variant (c.98807G > A; p.Arg32936His) in the TTN gene in the index patients. No heterozygous individuals in the family presented LGMD features. The variant p.Arg32936His leads to a substitution of the arginine amino acid at position 32,936 into histidine possibly causing LGMD type 10. Conclusion We identified a homozygous missense variant in TTN, which likely explains LGMD type 10 in this family in line with similar previously reported data. Our study concludes that WES is a successful molecular diagnostic tool to identify pathogenic variants in large genes such as TTN in highly inbred population.

3-M syndrome – a primordial short stature disorder with novel CUL7 mutation in two Indian patients

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Radha Rama Devi Akella
Keyword(s):  
Short Stature ◽  
Autosomal Recessive ◽  
Genetic Diagnosis ◽  
Autosomal Recessive Disorder ◽  
Missense Variant ◽  
Postnatal Growth ◽  
Compound Heterozygous ◽  
Case Presentation ◽  
Whole Exome ◽  
Heterozygous Variant

Abstract Objective To evaluate the cause of short stature in children. Case presentation Two children with suspected skeletal dysplasia and short stature were evaluated. Conclusions The 3-M syndrome is a primordial growth disorder manifesting severe postnatal growth restriction, skeletal anomalies and prominent fleshy heels. The 3-M syndrome is a genetically heterogeneous disorder and the phenotype is similar. This is a rare autosomal recessive disorder with normal intellect. Two affected children have been identified by whole-exome sequencing. One patient harboured a compound heterozygous variant and the other was a homozygous missense variant. The genetic diagnosis helped in counselling the families and facilitated prenatal diagnosis in one (case 1) family.

scholarly journals Hereditary spastic paraplegia:Pathogenesis and pathophysiology

2018 ◽  
pp. 1-13
Author(s):  
Akgun Olmez ◽  
Haluk Topaloglu
Keyword(s):  
Genetic Testing ◽  
Corpus Callosum ◽  
Hereditary Spastic Paraplegia ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Spastic Paraplegia ◽  
Thin Corpus Callosum ◽  
Hereditary Spastic Paraplegias ◽  
Recessive Type ◽  
Mitochondrial Functions

Hereditary spastic paraplegias constitute a larger group of disorders than expected. Autosomal dominant types are mainly composed of SPAST, Atlastin (SPG3A) and REEP1 Genetic testing is suggested mainly for these genes. The most common autosomal recessive type is SPG11, hereditary spastic paraplegia with thin corpus callosum, but SPG15 shares the same clinical features with SPG11. Genetic testing should be done for both if thin corpus callosum is present in patients. How different genes with many different biological functions, including axonal transport, mitochondrial functions, fatty acid and cholesterol pathways and DNA repair defects, cause hereditary spastic paraplegia is still unknown.

Carbonic anhydrase VA deficiency: a very rare case of hyperammonemic encephalopathy

2020 ◽  
Vol 33 (10) ◽  
pp. 1349-1352
Author(s):  
Asburce Olgac ◽  
Cigdem Seher Kasapkara ◽  
Mustafa Kilic ◽  
Ebru Yılmaz Keskin ◽  
Gonca Sandal ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Inborn Error ◽  
Autosomal Recessive ◽  
Normal Development ◽  
Metabolic Decompensation ◽  
Case Presentation ◽  
Hyperammonemic Encephalopathy ◽  
Whole Exome ◽  
Elevated Lactate ◽  
Biochemical Features

AbstractObjectivesCarbonic anhydrase VA (CAVA) deficiency is a rare autosomal recessive inborn error of metabolism that leads to acute metabolic crises, especially in the neonatal or infantile period. It is caused by a deficiency of the enzyme CAVA, which is encoded by the CA5A gene.Case presentationFifteen patients with homozygous pathogenic CA5A mutations involving 10 different lesions have been reported in the literature up to date. Main clinical and biochemical features of CAVA deficiency include lethargy, hyperammonemic encephalopathy, metabolic acidosis, elevated lactate and hypoglycemia. In most patients reported so far, a single metabolic decompensation attack has been reported, and they have remained stable thereafter with no further crisis.ConclusionsWe report the 16th case of CAVA deficiency, who was diagnosed by whole-exome sequencing and showed a typical course of the disease with normal development at 18 months.

scholarly journals Childhood Seeligmüller Strümpell Philip Disease: The First Case in Iraq and a Review of the Early Historic Documentation of the Disease in the Literature

2020 ◽  
Vol 2 (2) ◽  
pp. 52-55
Author(s):  
Al-Mosawi AJ
Keyword(s):  
Lupus Erythematosus ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Brain Mri ◽  
Clinical Findings ◽  
Spastic Paraplegia ◽  
Evidence Based Treatment ◽  
First Case ◽  
Medical City ◽  
Early Historic

Seeligmüller Strümpell Philip disease is characterized by familial progressive spastic paraplegia or paraparesis associated with a progressive deterioration of gait. The disorder is genetically heterogeneous and can be inherited in an autosomal dominant, autosomal recessive or X-linked recessive manner. The mode of inheritance involved has a direct impact on the chances of inheriting the disorder. The cornerstone of treatment is the use of various muscle relaxants. The disorder has not been reported or documented in Iraq. This paper aims to report the first case of childhood Seeligmüller Strümpell Philip disease in an Iraqi girl. Patients and Methods: A thirteen-year girl with childhood Seeligmüller Strümpell Philip disease who developed systemic lupus erythematosus is described and the early historic documentation of Seeligmüller Strümpell Philip disease in the medical literature is briefly updated. Results: The diagnosis of Seeligmüller Strümpell Philip disease in this girl was based on clinical findings and supported by electromyography and nerve conduction studies. Brain MRI showed normal findings. Few weeks before the patient was seen, they took her outside Iraq to Medipol Mega complex of Hospitals for treatment. They performed tenotomy and tenoplasty of the hip adductors, achilloplasty, and posterior capsule relaxation. When the girl was first seen at the Children Teaching Hospital of Baghdad Medical City, the parents regretted taking her outside Iraq for treatment as she didn’t show any improvement, and was still using the wheelchair. Conclusion: Unfortunately, the girl was seen too late, and despite consulting many doctors in Iraq and outside Iraq, she didn’t receive appropriate evidence based treatment and was treated unsatisfactorily surgically.

scholarly journals Two novel compound heterozygous variants of LTBP4 in a Chinese infant with cutis laxa type IC and a review of the related literature

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Qiang Zhang ◽  
Zailong Qin ◽  
Shang Yi ◽  
Hao Wei ◽  
Xun Zhao Zhou ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Retinal Hemorrhage ◽  
Cutis Laxa ◽  
Compound Heterozygous ◽  
Case Presentation ◽  
Whole Exome ◽  
Analytical Review ◽  
Different Populations ◽  
Compound Heterozygous Variants ◽  
Chromosome 19Q13

Abstract Background Autosomal recessive cutis laxa type IC (ARCL IC, MIM: #613177) results from a mutation in the LTBP4 gene (MIM: #604710) on chromosome 19q13. Case presentation A 28-day-old Chinese infant with generalized cutis laxa accompanied by impaired pulmonary, gastrointestinal, genitourinary, retinal hemorrhage, abnormality of coagulation and hyperbilirubinemia was admitted to our hospital. To find out the possible causes of these symptoms, whole-exome sequencing was performed on the infant. Two novel pathogenic frame-shift variants [c.605_606delGT (p.Ser204fs * 8) and c.1719delC (p.Arg574fs * 199)] of the LTBP4 gene associated with ARCL IC were found which was later verified by Sanger sequencing. The pathogenicity of mutations was subsequently assessed by several software programs and databases. In addition, an analytical review on the clinical phenotypes of the disease previously reported in literature was performed. Conclusions This is the first report of a Chinese infant with ARCL IC in China due to novel pathogenic variations of LTBP4. Our study extends the cutis laxa type IC mutation spectrum as well as the phenotypes associated with the disease in different populations.

scholarly journals Homozygous truncating NEK10 mutation, associated with primary ciliary dyskinesia: a case report

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Fuad Al Mutairi ◽  
Randa Alkhalaf ◽  
Abdullah Alkhorayyef ◽  
Fayhan Alroqi ◽  
Alyafee Yusra ◽  
...  
Keyword(s):  
Primary Ciliary Dyskinesia ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Molecular Testing ◽  
Case Presentation ◽  
Immotile Cilia ◽  
Whole Exome ◽  
Novel Variant ◽  
Pathophysiological Aspect ◽  
Ciliary Dyskinesia

Abstract Background Primary Ciliary Dyskinesia (PCD) is also known as immotile-cilia syndrome, an autosomal recessive disorder of ciliary function, leading to mucus retention in the respiratory system in childhood. Our knowledge in the pathophysiological aspect of this devastating disorder is increasing with the advancement of genetic and molecular testing. Case presentation Here in, we report two siblings with a classical clinical and radiological presentation of PCD. Using whole exome sequencing we identified a homozygous truncating variant (c.3402 T > A); p.(Tyr1134*) in the NEK10 gene. Western bolt analysis revealed a decrease in the expression of NEK10 protein in the patient cells. Conclusions NEK10 plays a central role in the post-mitotic process of cilia assembly, regulating ciliary length and functions during physiological and pathological status. This study highlights the challenges of identifying disease-causing variants for a highly heterogeneous disorder and reports on the identification of a novel variant in NEK10 which recently associated with PCD.

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