ABO*B.01+c.464A>C represents a missense variation in the ABO gene and encodes a weak B phenotype

Transfusion ◽  
2021 ◽  
Author(s):  
Chenchen Feng ◽  
Hui Li ◽  
Taixiang Liu ◽  
Jianyu Xiao ◽  
Chengyin Huang ◽  
...  
Keyword(s):  
Missense Variation

Bilateral Striatal Necrosis with Polyneuropathy with a Novel SLC25A19 (Mitochondrial Thiamine Pyrophosphate Carrier OMIMI*606521) Mutation: Treatable Thiamine Metabolic Disorder—A Report of Two Indian Cases

2019 ◽  
Vol 50 (05) ◽  
pp. 313-317 ◽  
Author(s):  
Vykuntaraju K. Gowda ◽  
Varunvenkat M. Srinivasan ◽  
Kapil Jehta ◽  
Maya D. Bhat
Keyword(s):  
Gene Mutations ◽  
Febrile Illness ◽  
Flaccid Paralysis ◽  
Thiamine Pyrophosphate ◽  
Homozygous Mutation ◽  
Missense Variation ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain ◽  
Generation Sequencing ◽  
Striatal Necrosis

Abstract Background SLC25A19 gene mutations cause Amish congenital lethal microcephaly and bilateral striatal necrosis with polyneuropathy. We are reporting two cases of bilateral striatal necrosis with polyneuropathy due to SLC25A19 gene mutations. Methods A 36-month-old boy and a 5-year-old girl, unrelated, presented with recurrent episodes of flaccid paralysis and encephalopathy following nonspecific febrile illness. Examination showed dystonia and absent deep tendon reflexes. Results Nerve conduction studies showed an axonal polyneuropathy. Magnetic resonance imaging (MRI) of the brain in both cases showed signal changes in the basal ganglia. Next-generation sequencing revealed a novel homozygous missense variation c.910G>A (p.Glu304Lys) in the SLC25A19 gene in the boy and a homozygous mutation c.869T > A (p. Leu290Gln) in the SLC25A19 gene in the girl. Mutations were validated by Sanger sequencing, and carrier statuses of parents of both children were confirmed. Both children improved with thiamine supplementation. Conclusion If any child presents with recurrent encephalopathy with flaccid paralysis, dystonia, and neuropathy, a diagnosis of bilateral striatal necrosis with polyneuropathy due to SLC25A19 mutations should be considered and thiamine should be initiated.

scholarly journals Novel USH1G homozygous variant underlying USH2-like phenotype of Usher syndrome

2019 ◽  
pp. 112067211987939
Author(s):  
Fabiana D’Esposito ◽  
Viviana Randazzo ◽  
Gilda Cennamo ◽  
Nicola Centore ◽  
Paolo Enrico Maltese ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Retinitis Pigmentosa ◽  
Sensorineural Hearing Loss ◽  
Hearing Impairment ◽  
Usher Syndrome ◽  
Age At Onset ◽  
Vestibular Dysfunction ◽  
Sensorineural Hearing ◽  
Type I ◽  
Missense Variation

Purpose: Usher syndrome (USH) is an autosomal recessive disorder characterized by congenital sensorineural hearing impairment and retinitis pigmentosa. Classification distinguishes three clinical types of which type I (USH1) is the most severe, with vestibular dysfunction as an added feature. To date, 15 genes and 3 loci have been identified with the USH1G gene being an uncommon cause of USH. We describe an atypical USH1G-related phenotype caused by a novel homozygous missense variation in a patient with profound hearing impairment and relatively mild retinitis pigmentosa, but no vestibular dysfunction. Methods: A 26-year-old female patient with profound congenital sensorineural hearing loss, nyctalopia and retinitis pigmentosa was studied. Audiometric, vestibular and ophthalmologic examination was performed. A panel of 13 genes was tested by next-generation sequencing (NGS). Results: While the hearing loss was confirmed to be profound, the vestibular function resulted normal. Although typical retinitis pigmentosa was present, the age at onset was unusually late for USH1 syndrome. A novel homozygous missense variation (c.1187T>A, p.Leu396Gln) in the USH1G gene has been identified as causing the disease in our patient. Conclusions: Genetic and phenotypic heterogeneity are very common in both isolated and syndromic retinal dystrophies and sensorineural hearing loss. Our findings widen the spectrum of USH allelic disorders and strength the concept that variants in genes that are classically known as underlying one specific clinical USH subtype might result in unexpected phenotypes.

An X‐linked syndrome with severe neurodevelopmental delay, hydrocephalus, and early lethality caused by a missense variation in the OTUD5 gene

2020 ◽  
Author(s):  
Kornelia Tripolszki ◽  
Erina Sasaki ◽  
Ronja Hotakainen ◽  
Abdul Halim Kassim ◽  
Catarina Pereira ◽  
...  
Keyword(s):  
Neurodevelopmental Delay ◽  
Missense Variation ◽  
Early Lethality

scholarly journals Functional characterization of 3D protein structures informed by human genetic diversity

2019 ◽  
Vol 116 (18) ◽  
pp. 8960-8965 ◽  
Author(s):  
Michael Hicks ◽  
Istvan Bartha ◽  
Julia di Iulio ◽  
J. Craig Venter ◽  
Amalio Telenti
Keyword(s):  
Large Scale ◽  
Functional Characterization ◽  
Protein Structures ◽  
Large Scale Data ◽  
Allosteric Sites ◽  
Missense Variation ◽  
Binding Pockets ◽  
Definition Of ◽  
Scale Data

Sequence variation data of the human proteome can be used to analyze 3D protein structures to derive functional insights. We used genetic variant data from nearly 140,000 individuals to analyze 3D positional conservation in 4,715 proteins and 3,951 homology models using 860,292 missense and 465,886 synonymous variants. Sixty percent of protein structures harbor at least one intolerant 3D site as defined by significant depletion of observed over expected missense variation. Structural intolerance data correlated with deep mutational scanning functional readouts for PPARG, MAPK1/ERK2, UBE2I, SUMO1, PTEN, CALM1, CALM2, and TPK1 and with shallow mutagenesis data for 1,026 proteins. The 3D structural intolerance analysis revealed different features for ligand binding pockets and orthosteric and allosteric sites. Large-scale data on human genetic variation support a definition of functional 3D sites proteome-wide.

Factor VII gene intronic mutation in a lethal factor VII deficiency: effects on splice-site selection

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 561-563 ◽  
Author(s):  
Keren Borensztajn ◽  
Marie-Laure Sobrier ◽  
Anne-Marie Fischer ◽  
Ouerdia Chafa ◽  
Serge Amselem ◽  
...  
Keyword(s):  
Splice Site ◽  
Stop Codon ◽  
Lethal Factor ◽  
Variable Number ◽  
Factor Vii ◽  
Nucleotide Substitutions ◽  
Splice Site Selection ◽  
Intronic Mutation ◽  
Missense Variation ◽  
Mutant Construct

AbstractIn a patient with lethal factor VII (FVII) deficiency, 2 homozygous nucleotide substitutions were identified in the F7 gene: a IVS7+2T>G transversion involving the IVS7 donor splice site, followed by a mutation at nucleotide 10588 that would result in a missense variation (Arg224Gln). The mutated splice site, located within the first repeat of a minisatellite, is followed by a variable number of pseudo-sites, normally silent. To investigate the consequences of this mutation on F7 splicing, we designed normal and mutant minigenes, spanning exons 5 to 8. In cells transfected with the mutant construct, no normal splicing occurred. Only spliced transcripts including the first minisatellite repeat were observed, resulting from the activation of the most proximal wild-type pseudo-site, which would generate a truncated protein (stop codon upstream of nucleotide 10588). These findings, which suggest the existence of a mechanism selecting one single splice site among multiple cryptic sites, explain the patient's phenotype.

scholarly journals GPRASP2, a novel causative gene mutated in an X-linked recessive syndromic hearing loss

2017 ◽  
Vol 54 (6) ◽  
pp. 426-430 ◽  
Author(s):  
Guangqian Xing ◽  
Jun Yao ◽  
Chunyu Liu ◽  
Qinjun Wei ◽  
Xuli Qian ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Gene Mutation ◽  
In Silico ◽  
In Silico Analysis ◽  
Chinese Family ◽  
Causative Gene ◽  
Genetic Hearing Loss ◽  
Missense Variation ◽  
Multiple Structures ◽  
Syndromic Hearing Loss

BackgroundA substantial amount of nuclear genes have been identified to be implicated in genetic hearing loss, while X-linked hearing loss is genetically heterogeneous and relatively infrequent.ObjectiveTo identify the causative gene mutation in a five-generation Chinese family with an X-linked recessive syndromic hearing loss (SHL).MethodsTargeted X-chromosome exome sequencing was conducted, and cosegregation analysis was performed in the members of the affected family. The in silico and expression studies were also performed.ResultsA 2-bp missense mutation (c.1717_1718GC>AA, p.A573N) in the G protein-coupled receptor associated sorting protein 2 (GPRASP2) gene was identified in four hemizygous male patients and two heterozygous female carriers, which was cosegregated with the clinical phenotypes in this family. In silico analysis supported that this gene mutation is functionally deleterious, and it was detected that homologousGprasp2was highly expressed in multiple structures of the mouse cochlea, which suggested thatGPRASP2might be the genetic cause for the described disease phenotypes.ConclusionsThis study presented a novel X-linked SHL combined with unique and unrecognised clinical features, and a missense variation ofGPRASP2was first identified to be implicated in X-linked SHL.

scholarly journals Exertional Heat Stroke and Susceptibility to Malignant Hyperthermia in an Athlete: Evidence for a Link?

2015 ◽  
Vol 50 (11) ◽  
pp. 1212-1214 ◽  
Author(s):  
Mathias Poussel ◽  
Philippe Guerci ◽  
Pierre Kaminsky ◽  
Marie Heymonet ◽  
Nathalie Roux-Buisson ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Oxidative Metabolism ◽  
Heat Stroke ◽  
Return To Sport ◽  
Fresh Frozen Plasma ◽  
Multiple Organ ◽  
Exertional Heat Stroke ◽  
Ryr1 Gene ◽  
Missense Variation ◽  
Fresh Frozen

Objective  To describe the possible association (pathophysiologic and clinical features) between exertional heat stroke (EHS) and malignant hyperthermia (MH). Background  Both EHS and MH are acute and life-threatening disorders. It has repeatedly been shown that EHS can occur in well-trained patients with known MH-associated mutation in the RYR1 gene in the absence of any extreme environmental conditions or extreme physical activity, thereby supporting a possible link between EHS and MH. In this case, a highly trained 30-year-old male athlete suddenly collapsed while running. He had initial hyperthermia (40.2°C) and progressive multiple organ failure requiring medical management in an intensive care unit. After he recovered completely, a maximal exercise test was performed and showed an obvious abnormality of oxidative metabolism in muscle; genetic analysis of the RYR1 gene identified a heterozygous missense variation p.K1393R. Consequently, the athlete was given appropriate information and allowed to progressively return to sport competition. Differential Diagnosis  Doping, use of drugs and toxic agents, exercise-associated hyponatremia, exertional heat illness. Treatment  Initial management started with the basic resuscitative guidelines of airway, breathing, and circulation (intubation). Cooling, administration of fresh frozen plasma, and intensive rehydration resulted in improvement. Uniqueness  To our knowledge, ours is the first description of this MH mutation (p.K1393R) in the RYR1 gene that was associated with exertional rhabdomyolysis involving a dramatic impairment of oxidative metabolism in muscle. Conclusions  Common features are shared by EHS and MH. Careful attention must therefore be paid to athletes who experience EHS, especially in temperate climates or when there are no other predisposing factors.

Double Heterozygous Mutations (Cys247Tyr and 252delAsn) Cause Factor XII Deficiency in a Chinese Family

2020 ◽  
Vol 40 (05) ◽  
pp. 650-654
Author(s):  
Yu Wang ◽  
Haiyue Zhang ◽  
Siqi Liu ◽  
Jiajia Ye
Keyword(s):  
Coagulation Factor ◽  
Activated Partial Thromboplastin Time ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chinese Family ◽  
Factor Xii ◽  
Heterozygous Deletion ◽  
Factor Xii Deficiency ◽  
The World ◽  
Missense Variation ◽  
Exon 9

Abstract Objective To study the molecular basis of human coagulation factor XII (FXII) deficiency in a Chinese family. Methods Routine blood coagulation indexes were detected by a one-stage clotting method, whereas FXII antigen was detected by enzyme linked immunosorbent assay. DNA sequencing was applied to find mutations in the F12 gene. Bioinformatics and conservative analyses were performed to analyze possible effects of the mutation. Results The proband had significantly prolonged activated partial thromboplastin time (141.9 seconds), and her FXII clotting activity was decreased to 5%. Genetic analysis revealed that the propositus carried a heterozygous missense mutation c.797G > A in exon 8 resulting in Cys247Tyr and deletion mutation c.809_811delACA in exon 9 resulting in 252delAsn. Bioinformatics results indicated that the mutation had affected the function of the protein. Conclusion The c.797G > A heterozygous missense variation and the c.809_811delACA heterozygous deletion variation are associated with decreased FXII levels in this family, of which c.797G > A is first reported in the world.

scholarly journals Homozygous Recessive Versican Missense Variation Is Associated With Early Teeth Loss in a Pakistani Family

2019 ◽  
Vol 9 ◽  
Author(s):  
Stefania Bigoni ◽  
Marcella Neri ◽  
Chiara Scotton ◽  
Roberto Farina ◽  
Patrizia Sabatelli ◽  
...  
Keyword(s):  
Pakistani Family ◽  
Missense Variation
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