scholarly journals Heterozygous VPS13A and PARK2 Mutations in a Patient with Parkinsonism and Seizures

2021 ◽  
pp. 341-346
Author(s):  
Steven D. Mitchell ◽  
Roger L. Albin ◽  
William T. Dauer ◽  
John L. Goudreau ◽  
Christos Sidiropoulos
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Clinical Symptoms ◽  
Phenotypic Diversity ◽  
Phenotypic Expression ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Epistatic Interactions ◽  
History Of ◽  
Vacuolar Protein

Neuroacanthocytosis (NA) is a diverse group of disorders in which nervous system abnormalities co-occur with irregularly shaped red blood cells called acanthocytes. Chorea-acanthocytosis is the most common of these syndromes and is an autosomal recessive disease caused by mutations in the <i>vacuolar protein sorting 13A</i> (VPS13A) gene. We report a case of early onset parkinsonism and seizures in a 43-year-old male with a family history of NA. Neurologic examinations showed cognitive impairment and marked parkinsonian signs. MRI showed bilateral basal ganglia gliosis. He was found to have a novel heterozygous mutation in the VPS13A gene, in addition a heterozygous mutation in the PARK2 gene. His clinical picture was atypical for typical chorea-acanthocytosis (ChAc). The compound heterozygous mutations of VPS13A and PARK2 provide the most plausible explanation for this patient’s clinical symptoms. This case adds to the phenotypic diversity of ChAc. More research is needed to fully understand the roles of epistatic interactions on phenotypic expression of neurodegenerative diseases.

scholarly journals Novel compound heterozygous mutation in SACS gene leads to a milder autosomal recessive spastic ataxia of Charlevoix‐Saguenay, ARSACS , in a Finnish family

2016 ◽  
Vol 4 (12) ◽  
pp. 1151-1156 ◽  
Author(s):  
Johanna Palmio ◽  
Mikko Kärppä ◽  
Peter Baumann ◽  
Sini Penttilä ◽  
Jukka Moilanen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Spastic Ataxia

scholarly journals Complex medical history of a patient with a compound heterozygous mutation in C1QC

Lupus ◽  
2019 ◽  
Vol 28 (10) ◽  
pp. 1255-1260 ◽  
Author(s):  
R Lubbers ◽  
L J J Beaart-van de Voorde ◽  
K van Leeuwen ◽  
M de Boer ◽  
K A Gelderman ◽  
...  
Keyword(s):  
Western Blot ◽  
Medical History ◽  
Rna Sequencing ◽  
Lupus Erythematosus ◽  
Compound Heterozygous Mutation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Classical Pathway ◽  
History Of

Introduction C1q is an essential part of the classical pathway of complement activation. Genetic deficiencies, caused by homozygous mutations in one of the C1q genes, are rare and are strongly associated with development of systemic lupus erythematosus (SLE). Here we describe a C1q-deficient patient with a compound heterozygous mutation. Material and methods Serum was analysed with enzyme-linked immunosorbent assay (ELISA) and Western blot for the presence of C1q, and DNA and RNA sequencing was performed to identify the mutations and confirm that these were located on different chromosomes. Results The medical history of the patient includes SLE diagnosis at age 11 years with cerebral involvement at age 13, various infections, osteonecrosis and hemophagocytic syndrome. Using ELISA and Western blot, we confirmed the absence of C1q in the serum of the patient. Using DNA sequencing, two mutations in the C1QC gene were identified: c.100G > A p.(Gly34Arg) and c.205C > T p.(Arg69X). With RNA sequencing we confirmed that the mutations are located on different chromosomes. Discussion The patient described in this case report has a compound heterozygous mutation in C1QC resulting in C1q deficiency.

Mutations in BTD gene causing biotinidase deficiency: a regional report

2015 ◽  
Vol 28 (3-4) ◽  
Author(s):  
Çiğdem Seher Kasapkara ◽  
Melek Akar ◽  
Mehmet Nuri Özbek ◽  
Heybet Tüzün ◽  
Bedri Aldudak ◽  
...  
Keyword(s):  
Inborn Error ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Biotinidase Deficiency ◽  
Compound Heterozygous ◽  
Metabolic Abnormalities ◽  
Base Pairs ◽  
Cutaneous Manifestations ◽  
Toxic Metabolites ◽  
Untreated Individuals

AbstractBiotinidase deficiency is an autosomal recessive inborn error of biotin metabolism. Children with biotinidase deficiency cannot cleave biocytin and, therefore, cannot recycle biotin. Untreated individuals become secondarily biotin deficient, which in turn results in decreased activities of the biotin-dependent carboxylases and the subsequent accumulation of toxic metabolites causing clinical symptoms. Biotinidase deficiency is characterized by neurological, cutaneous manifestations and metabolic abnormalities. The worldwide incidence of profound biotinidase deficiency has been estimated at 1:112,271. The human biotinidase gene is located on chromosome 3p25 and consists of four exons with a total length of 1629 base pairs. To date, more than 100 mutations in the biotinidase gene known to cause biotinidase deficiency have been reported. The vast majority of mutations are homozygous or compound heterozygous. Finding known mutations can be correlated with the biochemical enzymatic results. This report summarizes the demographic features of patients identified as biotinidase deficient from August of 2012 through August of 2013 and mutation analysis results for 20 cases in the southeast region of Turkey.

scholarly journals ASTHMA IN CYSTIC FIBROSIS

2015 ◽  
Vol 64 (2) ◽  
pp. 118-121
Author(s):  
Marcela Daniela Ionescu ◽  
◽  
Ioana-Alina Anca ◽  
Mihaela Balgradean ◽  
◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Airway Obstruction ◽  
Autosomal Recessive ◽  
Pulmonary Infection ◽  
Autosomal Recessive Disease ◽  
Personal History ◽  
Common Symptom ◽  
Infection And Inflammation ◽  
History Of

Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians. Lung disease is characterized by impaired mucocilliary clearance with airway obstruction and chronic pulmonary infection and inflammation. Wheeze is a common symptom in CF, but in some cases the wheeze is due to the presence of concomitant asthma. There is no consensus on how to define CF asthma, but the diagnosis is predominantly based on the patient’s strong family and personal history of atopy.

scholarly journals Novel compound heterozygous mutation in WEE2 is associated with fertilization failure: case report of an infertile woman and literature review

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ye Tian ◽  
Guojie Wang ◽  
Jin Wang ◽  
Xiaohuan Mu ◽  
Haixia Chen ◽  
...  
Keyword(s):  
Donor Site ◽  
Oocyte Retrieval ◽  
Controlled Ovarian Hyperstimulation ◽  
Infertile Woman ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Fertilization Failure ◽  
Whole Exome ◽  
History Of

Abstract Background Fertilization failure after intracytoplasmic sperm injection continues to affect couples and the etiology is not well-understood. Case presentation We characterized a couple with 2-year history of primary unexplained infertility. Three different assisted reproduction attempts (IVF + rescue ICSI, ICSI and ICSI-AOA) showed repeated fertilization failure for MII oocyte retrieval after controlled ovarian hyperstimulation. After whole-exome sequencing and sanger sequencing of the couple and their family members, variant pathogenicity was assessed using SIFT, PolyPhen2, Mutation Taster, and Human Splicing Finder software. We identified novel compound heterozygous mutations, c.1535 + 3A > G and c.946C > T (p. Leu316Phe), in WEE2 in the female proband. Trios analysis of the variations revealed an autosomal recessive pattern. c.1535 + 3A > G in WEE2 was predicted to break the wild-type donor site and affect splicing, and the missense mutation c.946C > T (p. Leu316Phe) of WEE2 was predicted to be pathogenic. Conclusion A novel compound heterozygous mutation in WEE2 was identified in an infertile female who experienced repeated fertilization failure even after ICSI-AOA. These novel mutations in WEE2 provided genetic evidence for fertilization failure.

UNC13D and PRF1 Mutations in Childhood Patients with Hemophagocytic Lymphohistiocytosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1334-1334
Author(s):  
Udo zur Stadt ◽  
Karin Beutel ◽  
Florian Oyen ◽  
A. Sarper Diler ◽  
Hartmut Kabisch ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Autosomal Recessive ◽  
Genetic Defect ◽  
Geographic Origin ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Single Mutation ◽  
Nonsense Mutations ◽  
Coding Regions ◽  
Gene Defects

Abstract Introduction: Familial Hemophagocytic Lymphohistiocytosis (FHLH) is an autosomal recessive disease affecting young children. It manifests itself as a severe hyperinflammatory syndrome with activated macrophages and T-lymphocytes. Mutations in Perforin (PRF1) are responsible for FHL-2 in about 15 to 50 % of the patients. Defective granule exocytosis due to mutations in UNC13D have recently been described as the genetic defect underlying FHL-3. Both types are phenotypically not distinguishable from one another. Patients and Methods: Genetic analysis was performed in either the 2 or the 32 exons of PRF1 and UNC-13D, respectively, in 61 patients with hemophagocytic lymphohistiocytosis (HLH) of different geographic origin (28 from Germany, 24 from Turkey and 9 from other countries). Results: We identified mutations in 28 samples investigated (18 in PRF1, 10 in UNC-13D). Besides several known mutations novel deletions, missense and nonsense mutations were detected in both genes scattering the whole coding regions. The Trp374stop mutation (11/13 patients with a PRF1 mutation from Turkey) was the only single mutation repeatedly observed in several patients with a common geographic origin. In HLH patients from Germany, 7/28 patients showed homozygous or compound heterozygous mutations in either PRF1 (3) or UNC13D (4). In 24 HLH patients from Turkey 13 patients with a mutation in PRF1 and 4 patients with a mutation in UNC13D were identified. In addition, four out of 9 patients with a different geographic origin showed mutations in one of this genes. In 10 patients only one heterozygous mutation in UNC13D was detected so far. In these cases, control samples or regulatory regions of the gene have to be analysed to ascertain the relevance of the underlying mutation. Defect Turkey German Other All UNC13D 4 4 2 10 PRF1 13 3 2 18 Unknown 7 21 5 33 Discussion: Overall, UNC-13D and PRF1 mutations were detectable in 45% of the cases. Our results indicate that FHL-2 and FHL-3 account for more than 60% of the HLH cases of Turkish origin with only a small number involving UNC-13D. In contrast, gene defects were identified in only 25% of the patients with a German ancestry. This work was supported by the Foerdergemeinschaft Kinderkrebszentrum Hamburg e. V.

scholarly journals Case Report: Novel Homozygous Likely Pathogenic SCN1A Variant With Autosomal Recessive Inheritance and Review of the Literature

2021 ◽  
Vol 12 ◽  
Author(s):  
Ana Victoria Marco Hernández ◽  
Miguel Tomás Vila ◽  
Alfonso Caro Llopis ◽  
Sandra Monfort ◽  
Francisco Martinez
Keyword(s):  
Developmental Disorders ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Autosomal Recessive Inheritance ◽  
Febrile Seizures ◽  
Dravet Syndrome ◽  
Compound Heterozygous ◽  
Recessive Inheritance ◽  
Clinical Criteria ◽  
Febrile Seizures Plus

Dominant pathogenic variations in the SCN1A gene are associated with several neuro developmental disorders with or without epilepsy, including Dravet syndrome (DS). Conversely, there are few published cases with homozygous or compound heterozygous variations in the SCN1A gene. Here, we describe two siblings from a consanguineous pedigree with epilepsy phenotype compatible with genetic epilepsy with febrile seizures plus (GEFS+) associated with the homozygous likely pathogenic variant (NM_001165963.1): c.4513A &gt; C (p.Lys1505Gln). Clinical and genetic data were compared to those of other 10 previously published patients with epilepsy and variants in compound heterozygosity or homozygosity in the SCN1A gene. Most patients (11/12) had missense variants. Patients in whom the variants were located at the cytoplasmic or the extracellular domains frequently presented a less severe phenotype than those in whom they are located at the pore-forming domains. Five of the patients (41.7%) meet clinical criteria for Dravet syndrome (DS), one of them associated acute encephalopathy. Other five patients (41.7%) had a phenotype of epilepsy with febrile seizures plus familial origin, while the two remaining (17%) presented focal epileptic seizures. SCN1A-related epilepsies present in most cases an autosomal dominant inheritance; however, there is growing evidence that some genetic variants only manifest clinical symptoms when they are present in both alleles, following an autosomal recessive inheritance.

scholarly journals THE ROLE OF CONNECTIVE TISSUE DYSPLASIA IN CHILDREN’S CYSTIC FIBROSIS. CLINICAL AND GENETIC ASPECTS

2018 ◽  
Vol 63 (5) ◽  
pp. 20-28
Author(s):  
A. V. Goryainova ◽  
P. V. Shumilov ◽  
N. Yu. Kashirskaya ◽  
S. Yu. Semykin
Keyword(s):  
Cystic Fibrosis ◽  
Liver Fibrosis ◽  
Connective Tissue ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Clinical Manifestations ◽  
History Of ◽  
Connective Tissue Dysplasia ◽  
Severe Fibrosis

The article considers the issue of cystic fibrosis – a monogenic autosomal recessive disease. It describes the history of the CFTR gene discovery, the further search for modifier genes to explain the variability of the clinical manifestations of cystic fibrosis. The review discusses problems of connective tissue dysplasia and somatic pathology, which is formed due to the connective tissue dysmorphogenesis in patients with cystic fibrosis; and also the article contains justification for the connection between the formation of severe fibrosis of the lungs and liver and the presence of clinical and genetic markers of connective tissue dysplasia. The author assumes that the clinical and genetic polymorphisms of connective tissue influence the course of cystic fibrosis, formation of bronchiectasis, interstitial pneumofibrosis, cystic fibrosis dysplasia, liver fibrosis and cirrhosis.

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