scholarly journals Evaluation of a new variant in the aggrecan gene potentially associated with chondrodysplastic dwarfism in Miniature horses

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Danilo Giorgi Abranches de Andrade ◽  
Roberta Martins Basso ◽  
Angelo José Magro ◽  
Renée Laufer-Amorim ◽  
Alexandre Secorun Borges ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Amino Acid ◽  
Amino Acid Substitution ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Dwarf Phenotype ◽  
Horse Genome ◽  
Complex Interactions ◽  
New Variant ◽  
Exon 11

Abstract Chondrodysplastic dwarfism in Miniature horses is an autosomal recessive disorder previously associated with four mutations (D1, D2, D3*, and D4) in the aggrecan (ACAN) gene. The aim of this study was to identify additional variants in the candidate ACAN gene associated with chondrodysplastic dwarfism in Miniature horses. Fifteen dwarf Miniature horses were found to possess only one of the dwarfism-causing variants, and two possessed none of the variants. The ACAN exons (EquCab3.0) of seven dwarf Miniature horses were sequenced. A missense SNP in coding exon 11 (g.95271115A > T, c.6465A > T—RefSeq XM_005602799.2), which resulted in the amino acid substitution p.Leu2155Phe (RefSeq XP_005602856.2), was initially associated with the dwarf phenotype. The variant was tested and found present in 14 dwarf foals as well as one parent of each, and both parents of a dwarf possessing two copies. Genetic testing of 347 phenotypically normal Miniature horses demonstrated that none had more than one of the dwarf alleles or c.6465A > T. However, a study of large breeds revealed the presence of c.6465A > T, which was present in homozygosis in two Mangalarga Marchador horses. We suggest that c.6465A > T as a marker of disequilibrium or complex interactions in the Miniature horse genome could contribute to the associated dwarfism.

scholarly journals SAT-062 Twins with a Homozygous Variant of ARNT2, This Is a Known Saudi Mutation (KSM) of Webb- Dattani Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Abdullah Abdulruhman Aljasser
Keyword(s):  
Genetic Testing ◽  
Autosomal Recessive ◽  
Brain Mri ◽  
Autosomal Recessive Disorder ◽  
Cortical Blindness ◽  
High Signal ◽  
Thin Corpus Callosum ◽  
Homozygous Variant ◽  
Saudi Family ◽  
Delayed Myelination

Abstract Webb-Dattani syndrome (WEDAS) is an autosomal recessive disorder caused by mutation in the ARNT2 gene characterized by frontotemporal hypoplasia, globally delayed development, and pituitary and hypothalamic insufficiency. The condition is reported to be associated with consanguinity and with Saudi Arabian ancestry. We presented twin baby girls with developmental delayment seizures, and microcephaly. They have also hypopituitarism in the form of diabetes insipidus and hypocortlisim. also they have cortical blindness. Their brain MRI shows brain atrophic changes and delayed myelination thin corpus callosum,and small pituitary gland ad absence posterior high signal spot and pituitary stalk. Genetic testing by Exome sequencing was done and it shows A homozygous variant of ARNT2 (ARNT2:NM_014862:exon3:c.147-1G>A). One of this twin her condition deteriorated with uncontrolled seizures and spasticity and died at age 22 months. Conclusion: we report another cases of the ARNT2 mutation in a Saudi family illustrating the disease of webb-dattani Syndrome with seizures and hypopituitarism and severe visual impairment and global developmental delayment.

scholarly journals N-Acetylglutamate and its changing role through evolution

2003 ◽  
Vol 372 (2) ◽  
pp. 279-290 ◽  
Author(s):  
Ljubica CALDOVIC ◽  
Mendel TUCHMAN
Keyword(s):  
Amino Acid ◽  
Autosomal Recessive ◽  
Urea Cycle ◽  
Evolutionary Relationship ◽  
Autosomal Recessive Disorder ◽  
The Other ◽  
Arginine Biosynthesis ◽  
Carbamyl Phosphate ◽  
Carbamyl Phosphate Synthetase ◽  
Changing Role

N-Acetylglutamate (NAG) fulfils distinct biological roles in lower and higher organisms. In prokaryotes, lower eukaryotes and plants it is the first intermediate in the biosynthesis of arginine, whereas in ureotelic (excreting nitrogen mostly in the form of urea) vertebrates, it is an essential allosteric cofactor for carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle. The pathway that leads from glutamate to arginine in lower organisms employs eight steps, starting with the acetylation of glutamate to form NAG. In these species, NAG can be produced by two enzymic reactions: one catalysed by NAG synthase (NAGS) and the other by ornithine acetyltransferase (OAT). In ureotelic species, NAG is produced exclusively by NAGS. In lower organisms, NAGS is feedback-inhibited by l-arginine, whereas mammalian NAGS activity is significantly enhanced by this amino acid. The NAGS genes of bacteria, fungi and mammals are more diverse than other arginine-biosynthesis and urea-cycle genes. The evolutionary relationship between the distinctly different roles of NAG and its metabolism in lower and higher organisms remains to be determined. In humans, inherited NAGS deficiency is an autosomal recessive disorder causing hyperammonaemia and a phenotype similar to CPSI deficiency. Several mutations have been recently identified in the NAGS genes of families affected with this disorder.

Beta-ketothiolase deficiency brought with lethargy: Case report

2011 ◽  
Vol 30 (10) ◽  
pp. 1724-1727 ◽  
Author(s):  
Vefik Arica ◽  
Secil Gunher Arica ◽  
Huseyin Dag ◽  
Hatice Onur ◽  
Ömer Obut ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Case Report ◽  
Blood Glucose ◽  
Amino Acid ◽  
Ketone Body ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Branched Chain Amino Acid ◽  
Amino Acid Levels ◽  
Branched Chain

Beta-ketothiolase deficiency is a rare autosomal recessive disorder of isoleucine and ketone body metabolism. This disorder is clinically characterized by ketoacidotic attacks. Ketoacidosis, vomiting, and dehydration, lethargy and coma may be seen during attacks. A 9-month-old girl was admitted to our hospital with acidosis and dehydration. The patient was lethargic. Ketoacidosis was suspected because of acetone odor on her breath. Her blood glucose level was 262 mg/dL and urine ketone was (++++). Branched chain amino acid levels were elevated in her blood sample. Organic acid analysis of urine revealed 2-methylacetoacetyl-CoA thiolase deficiency. This was reported because of rarity of the disease and we should consider it in the differential diagnosis of ketoacidotic episodes.

scholarly journals Neurodegeneration with brain iron accumulation: A case report

2016 ◽  
Vol 10 (2) ◽  
pp. 160-164 ◽  
Author(s):  
Daniel Nassif ◽  
João Santos Pereira ◽  
Mariana Spitz ◽  
Cláudia Capitão ◽  
Alessandra Faria
Keyword(s):  
Case Report ◽  
Genetic Testing ◽  
Autosomal Recessive ◽  
Psychiatric Symptoms ◽  
Brain Mri ◽  
Autosomal Recessive Disorder ◽  
Iron Accumulation ◽  
Brain Iron ◽  
Diagnostic Importance ◽  
Abnormal Brain

ABSTRACT Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder caused by mutation in the PANK2 gene. It is characterized by abnormal brain iron accumulation, mainly in the globus pallidus. PKAN is included in a group of disorders known as neurodegeneration with brain iron accumulation (NBIA). We report a case of atypical PKAN with its most characteristic presentation, exhibiting marked psychiatric symptoms, speech disorder and focal dystonia. Brain MRI has great diagnostic importance in this group of disorders and, in this case, disclosed the eye-of-the-tiger sign. Genetic testing confirmed the diagnosis.

scholarly journals Congenital Dyserythropoietic Anemia Type 1: A New Variant Pathogenic CDAN1 Mutation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4551-4551 ◽  
Author(s):  
Jenny McDaniel ◽  
Stuart Cramer
Keyword(s):  
Bone Marrow ◽  
Amino Acid ◽  
Amino Acid Substitution ◽  
Sequence Variant ◽  
Type I ◽  
Red Cell ◽  
Female Fetus ◽  
Congenital Dyserythropoietic Anemia ◽  
Bone Marrow Evaluation ◽  
New Variant

Abstract Introduction: Congenital dyserythropoietic anemia (CDA) is a rare autosomal recessive condition that results in dyserythropoiesis and iron overload. Bone marrow evaluation in these patients demonstrates distinctive abnormalities in red cell precursors including multinucleated erythroblasts and chromatin bridges. Dysmorphisms such as distal limb abnormalities, skin pigmentation defects, vertebral malformations, and short stature may also be present. Mutations in the CDAN1/codanin-1 gene underlie the majority of CDA type I cases. We describe a previously unreported pathogenic variant. Case report: The female fetus of a gravida 2 para 1 woman was noted to have hepatomegaly, cardiomegaly, and elevated middle cerebral artery velocity concerning for severe intrauterine anemia at approximately 20 weeks gestation. The parents had one previous pregnancy that resulted in a stillborn male infant with hydrops fetalis and club foot. Given concern for anemia with this pregnancy, percutaneous umbilical cord blood sampling was performed demonstrating a fetal hematocrit of 9%. This severe fetal anemia was initially thought to be secondary to ABO incompatibility as mother was O- with a positive antibody screen and infant was A+. The fetus required four intrauterine transfusions and was delivered at 34 weeks 6 days via cesarean section due to history of previous cesarean. Exam revealed a phenotypically normal female with APGARs of 9/9 and a birth weight of 2130 grams. Following delivery the infant had serial blood counts performed over a 6-week period, which noted a steady decrease in her hematocrit to 16%. A transfusion was given, and a bone marrow evaluation revealed a cellular marrow with red cell hyperplasia and dyserythropoiesis. Next generation sequencing through PreventionGenetics was performed revealing a novel CDAN1 alteration. Results: The patient was found to be heterozygous for two mutations in trans in the CDAN1 gene: c.2072dupT and c.2093A>T. Discussion: We present a patient with severe fetal and infant transfusion dependent anemia who has two novel CDAN1 gene variants not previously described. The sequence variant c.2072dupT is predicted to result in a frameshift and premature protein termination and is expected to be pathogenic. The second variant c.2093A>T is predicted to result in an amino acid substitution (p.Glu698Val). Another amino acid substitution (p.Glu698Lys) was previously reported as pathogenic in an individual with congenital dyserythropoietic anemia. Based upon the clinical picture, morphologic characteristics, and genetic findings, we have concluded that this presentation is consistent with a diagnosis of CDA type I. Through the utilization of improved diagnostic techniques we continue to gain knowledge regarding the molecular underpinnings of CDA type I. Disclosures No relevant conflicts of interest to declare.

scholarly journals Analysis of the ARTIC version 3 and version 4 SARS-CoV-2 primers and their impact on the detection of the G142D amino acid substitution in the spike protein

2021 ◽  
Author(s):  
James Davis ◽  
Scott Wesley Long ◽  
Paul Christensen ◽  
Randall J Olsen ◽  
Robert Olson ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Drop Out ◽  
Spike Protein ◽  
Clinical Samples ◽  
New Variant ◽  
Common Resource ◽  
Improved Performance ◽  
Primer Sets ◽  
Public Repositories

The ARTIC Network provides a common resource of PCR primer sequences and recommendations for amplifying SARS-CoV-2 genomes. The initial tiling strategy was developed with the reference genome Wuhan-01, and subsequent iterations have addressed areas of low amplification and sequence drop out. Recently, a new version (V4) was released, based on new variant genome sequences, in response to the realization that some V3 primers were located in regions with key mutations. Herein, we compare the performance of the ARTIC V3 and V4 primer sets with a matched set of 663 SARS-CoV-2 clinical samples sequenced with an Illumina NovaSeq 6000 instrument. We observe general improvements in sequencing depth and quality, and improved resolution of the SNP causing the D950N variation in the spike protein. Importantly, we also find nearly universal presence of spike protein substitution G142D in Delta-lineage samples. Due to the prior release and widespread use of the ARTIC V3 primers during the initial surge of the Delta variant, it is likely that the G142D amino acid substitution is substantially underrepresented among early Delta variant genomes deposited in public repositories. In addition to the improved performance of the ARTIC V4 primer set, this study also illustrates the importance of the primer scheme in downstream analyses.

Genetic Analysis of Afibrinogenemia and Hypofibrinogenemia: Novel Mutations in the FGB Gene in the Turkish Population

2020 ◽  
Vol 143 (6) ◽  
pp. 529-532
Author(s):  
Didem Torun  Özkan ◽  
Nazan Sarper ◽  
Nejat Akar
Keyword(s):  
Amino Acid ◽  
Autosomal Recessive ◽  
Adenine Nucleotide ◽  
Gene Mutations ◽  
Autosomal Recessive Disorder ◽  
Turkish Population ◽  
Chain Gene ◽  
Congenital Afibrinogenemia ◽  
Low Levels ◽  
First Time

<b><i>Introduction:</i></b> Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Hypofibrinogenemia is characterized by fibrinogen levels &#x3c;1.5 g/L. <b><i>Objective:</i></b> In this study, we analyzed fibrinogen beta chain gene mutations in Turkish afibrinogenemia and hypofibrinogenemia patients. <b><i>Methods:</i></b> We evaluated 20 afibrinogenemia and hypofibrinogenemia patients and 80 healthy controls. We have sequenced all exons of the <i>FGB</i> gene using the DNA isolated from the peripheral blood samples of patients and controls. <b><i>Results and Conclusion:</i></b> We found a nonsense mutation in exon 4 at nucleotide 630 that encoded serine amino acid, and in the same exon a missense mutation of T to C at nucleotide 647, resulting in a transition from leucine to proline (p.L198P) in a child with hypofibrinogenemia. These mutations have been shown for the first time in the same patient of Turkish descent. Furthermore, there was a novel heterozygous guanine-to-adenine nucleotide change in exon 3. This caused the change of arginine amino acid to threonine amino acid at position 136 (p.A136T) in a protein, which has not been described in the literature before.

scholarly journals New Variant of CTX-M-Type Extended-Spectrum β-Lactamases, CTX-M-71, with a Gly238Cys Substitution in a Klebsiella pneumoniae Isolate from Bulgaria

2009 ◽  
Vol 53 (10) ◽  
pp. 4518-4521 ◽  
Author(s):  
Ines Schneider ◽  
Anne Marie Queenan ◽  
Rumyana Markovska ◽  
Boyka Markova ◽  
Emma Keuleyan ◽  
...  
Keyword(s):  
Amino Acid ◽  
Klebsiella Pneumoniae ◽  
Amino Acid Substitution ◽  
Hydrolytic Activity ◽  
Extended Spectrum ◽  
New Variant

ABSTRACT A single K lebsiella pneumoniae strain isolated in a Bulgarian hospital was found to produce CTX-M-71, a new CTX-M variant characterized by one amino acid substitution from glycine to cysteine at position 238 in comparison to CTX-M-15. This exchange decreased the hydrolytic activity of the β-lactamase for cefotaxime, ceftazidime, and cefepime.

scholarly journals Genetically proven fanconi anemia: a case report

2016 ◽  
Vol 4 (1) ◽  
pp. 290
Author(s):  
Rugmini Kamalammal ◽  
Divya Narayanan Kutty
Keyword(s):  
Case Report ◽  
Genetic Testing ◽  
Fanconi Anemia ◽  
Congenital Malformations ◽  
Rare Case ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Female Child ◽  
Clinical Findings ◽  
Genetic Studies

Fanconi anemia (FA) is a rare autosomal recessive disorder characterized by congenital malformations, haematological problems and predisposition to malignancies. It was first described by Guido Fanconi, a Swiss Paediatrician in 1927. The prevalence of FA is 1 to 5 cases per million.The genes that have been found to be mutated in FA patients are called FANC. 16 different FANC genes have been reported, among which 60-65% account for the mutations seen in FANCA genes which is the most frequently seen in FA patients. The disease is most commonly seen in children between 5-15 years. Diagnosis is based on the congenital physical abnormalities and confirmed by genetic testing. Here we report a rare case of Fanconi Anemia in a 4 year old female child with the characteristic clinical findings and the diagnosis was confirmed by genetic studies.  

scholarly journals Two Novel Heterozygote Mutations of ATM in a Chinese Family with Dystonia-Dominant Ataxia Telangiectasia and Literatures Review

2021 ◽  
Author(s):  
Zhijun Liu ◽  
Ming-Feng You ◽  
Ya-Ling Wang ◽  
Yan Xu
Keyword(s):  
Genetic Testing ◽  
Ataxia Telangiectasia ◽  
Clinical Characteristics ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Chinese Family ◽  
Initial Symptom ◽  
Clinical Heterogeneity ◽  
The Family ◽  
Dominant Ataxia

Abstract Ataxia-telangiectasia (A-T) is an autosomal recessive disorder with high clinical heterogeneity. A-T may present in complicated variable forms, mainly including classic A-T and milder forms. Contrary to the classic A-T, the milder form does not present the cardinal features of A-T, including ataxia and telangiectasia. A few ATM mutations have been reported in variant A-T cases manifested as isolated dystonia without any signs of classical A-T. To date, more than 400 disease-related ATM mutations have been identified in patients with A-T. In this study, target exome-sequencing was performed in an AT pedigree with predominant dystonia. Two novel ATM mutations, p.I2683T and p.S2860P, were identified in the family. We then reviewed previously published literatures of genetically confirmed A-T cases with predominant dystonia and summarized the clinical characteristics of dystonia-dominant A-T. To our knowledge, this is the first report of A-T patient with predominant dystonia in China. Dystonia may appear as one of the predominant manifestations or initial symptom of A-T. ATM genetic testing should be early considered for those patients with predominant dystonia, despite without accompanying ataxia or telangiectasia.

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