51,773 results match your criteria missense variant


The lysosomal protein ABCD4 can transport vitamin B across liposomal membranes in vitro.

J Biol Chem 2021 Apr 9:100654. Epub 2021 Apr 9.

Faculty of Pharmaceutical Sciences, Hiroshima International University, Kure, Japan.

Vitamin B (cobalamin) is an essential micronutrient for human health, and mutation and dysregulation of cobalamin metabolism are associated with serious diseases, such as methylmalonic aciduria and homocystinuria. Mutations in ABCD4 or LMBRD1, which encode the ATP-binding cassette (ABC) transporter ABCD4 and lysosomal membrane protein LMBD1, respectively, lead to errors in cobalamin metabolism, with the phenotype of a failure to release cobalamin from lysosomes. However, the mechanism of transport of cobalamin across the lysosomal membrane remains unknown. Read More

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Mutation spectrum and genotype-phenotype correlations in Chinese congenital ectopia lentis patients.

Exp Eye Res 2021 Apr 9:108570. Epub 2021 Apr 9.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China. Electronic address:

Purpose: To identify the spectrum and frequency of mutations in congenital ectopia lentis (CEL) and to investigate the correlations between genotype and clinical phenotype in Chinese CEL patients.

Methods: Ninety-three participants with CEL were enrolled from March 2017 to April 2020. Ocular and systemic examinations were performed for each included patient. Read More

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Dynamic analysis of CSF1R-related leukoencephalopathy on magnetic resonance imaging: a case report.

BMC Neurol 2021 Apr 10;21(1):156. Epub 2021 Apr 10.

Department of Neurology, Liuzhou People's Hospital, Liuzhou, China.

Background: Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare and rapidly progressive leukoencephalopathy characterized by cognitive, motor, and neuropsychiatric symptoms, which is often misdiagnosed. Magnetic resonance imaging (MRI) signs and follow-up MRI of CSF1R-related leukoencephalopathy could help in establishing a diagnosis, but these features are not widely known by general neurologists.

Case Presentation: A 34-year-old man was admitted for progressive weakness of the right limbs over 8 months. Read More

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AML-Associated Mutations in DNA Methyltransferase DNMT3A.

Biochemistry (Mosc) 2021 Mar;86(3):307-318

Faculty of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia.

In mammals, DNA methylation is an essential epigenetic modification necessary for the maintenance of genome stability, regulation of gene expression, and other processes. Carcinogenesis is accompanied by multiple changes in the DNA methylation pattern and DNA methyltransferase (DNMT) genes; these changes are often associated with poor disease prognosis. Human DNA methyltransferase DNMT3A is responsible for de novo DNA methylation. Read More

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Zinc transporter mutations linked to acrodermatitis enteropathica disrupt function and cause mistrafficking.

J Biol Chem 2021 Jan 8;296:100269. Epub 2021 Jan 8.

Department of Chemistry, Michigan State University, East Lansing, Michigan, USA; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USA. Electronic address:

ZIP4 is a representative member of the Zrt-/Irt-like protein (ZIP) transporter family and responsible for zinc uptake from diet. Loss-of-function mutations of human ZIP4 (hZIP4) drastically reduce zinc absorption, causing a life-threatening autosomal recessive disorder, acrodermatitis enteropathica (AE). These mutations occur not only in the conserved transmembrane zinc transport machinery, but also in the extracellular domain (ECD) of hZIP4, which is only present in a fraction of mammalian ZIPs. Read More

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January 2021

PIEZO1 mutation: a rare aetiology for fetal ascites.

BMJ Case Rep 2021 Apr 9;14(4). Epub 2021 Apr 9.

Maternal fetal Medicine, Trinity Health of New England, Hartford, Connecticut, USA.

We present a case of isolated fetal ascites diagnosed at 20 weeks' gestation. No aetiology was identified on extensive prenatal workup, including prenatal microarray. The patient terminated the pregnancy at 23 weeks' gestation. Read More

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Profiling of somatic mutations and fusion genes in acute myeloid leukemia patients with FLT3-ITD or FLT3-TKD mutation at diagnosis reveals distinct evolutionary patterns.

Exp Hematol Oncol 2021 Apr 9;10(1):27. Epub 2021 Apr 9.

Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.

Background: The receptor tyrosine kinase FLT3 with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) is a poor prognostic factor; however, the prognostic significance of missense mutation in the tyrosine kinase domain (FLT3-TKD) is controversial. Furthermore, the accompanying mutations and fusion genes with FLT3 mutations are unclear in acute myeloid leukemia (AML).

Methods: We investigated FLT3 mutations and their correlation with other gene mutations and gene fusions through two RNA-seq based next-generation sequencing (NGS) method and prognostic impact in 207 de novo AML patients. Read More

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Targeted next generation sequencing and family survey enable correct genetic diagnosis in CRX associated macular dystrophy - a case report.

BMC Ophthalmol 2021 Apr 9;21(1):168. Epub 2021 Apr 9.

Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

Background: We present 3 members of a family with macular dystrophy, originally diagnosed as Stargardt disease, with a significantly variable age at onset, caused by a heterozygous mutation in CRX.

Case Presentation: A 43-year-old female with bull's eye maculopathy, whose sister was diagnosed with Stargardt disease previously at another centre, was found to have a single ABCA4 variant. Further examination of the family revealed that the asymptomatic father was also affected, indicating a dominant pattern of inheritance. Read More

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Exome sequencing revealed PDE11A as a novel candidate gene for early-onset Alzheimer's disease.

Hum Mol Genet 2021 Apr 9. Epub 2021 Apr 9.

Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China.

To identify novel risk genes and better understand the molecular pathway underlying Alzheimer's disease (ad), whole-exome sequencing (WES) was performed in 215 early-onset ad (EOAD) patients and 255 unrelated healthy controls of Han Chinese ethnicity. Subsequent validation, computational annotation and in vitro functional studies were performed to evaluate the role of candidate variants in EOAD. We identified two rare missense variants in the phosphodiesterase 11A (PDE11A) gene in individuals with EOad. Read More

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Clinical and genetic analysis of classical Ehlers-Danlos syndrome patient caused by synonymous mutation in COL5A2.

Mol Genet Genomic Med 2021 Apr 8:e1632. Epub 2021 Apr 8.

Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, PR China.

Background: Classical Ehlers-Danlos syndrome (cEDS) is a heterogeneous connective tissue disorder that mainly results from the germline mutation of COL5A1 and COL5A2. The majority of the COL5A2 mutations reported to date represent structural mutations, including missense or in-frame exon-skipping splice mutations. The only reported synonymous mutation was expected to affect on splicing of exon 29 by prediction programs which should be further confirmed. Read More

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[Frontometaphyseal dysplasia 1 caused by variant of FLNA gene in a case].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Apr;38(4):355-358

Shanghai Chindren's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.

Objective: To explore the clinical and genetic characteristics of a child with frontometaphyseal dysplasia 1 (FMD1) due to variant of FLNA gene.

Methods: Clinical phenotype of the patient was analyzed. Whole exome sequencing (WES) was carried out to detect pathogenic genetic variants. Read More

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[Genetic analysis of three patients with Kleefstra syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Apr;38(4):347-350

Xianning Central Hospital (the First Affiliated Hospital of Hubei University of Science and Technology), Xianning, Hubei 437100, China.

Objective: To analyze the clinical and genetic features of three patient diagnosed with Kleefstra syndrome.

Methods: Whole exome sequencing (WES) was carried out for the probands and their parents. Suspected variants were validated by Sanger sequencing. Read More

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Respiratory complex and tissue lineage drive recurrent mutations in tumour mtDNA.

Nat Metab 2021 Apr 8. Epub 2021 Apr 8.

Computational Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Mitochondrial DNA (mtDNA) encodes protein subunits and translational machinery required for oxidative phosphorylation (OXPHOS). Using repurposed whole-exome sequencing data, in the present study we demonstrate that pathogenic mtDNA mutations arise in tumours at a rate comparable to those in the most common cancer driver genes. We identify OXPHOS complexes as critical determinants shaping somatic mtDNA mutation patterns across tumour lineages. Read More

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Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain.

Genet Med 2021 Apr 8. Epub 2021 Apr 8.

Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.

Purpose: We characterize the clinical and molecular phenotypes of six unrelated individuals with intellectual disability and autism spectrum disorder who carry heterozygous missense variants of the PRKAR1B gene, which encodes the R1β subunit of the cyclic AMP-dependent protein kinase A (PKA).

Methods: Variants of PRKAR1B were identified by single- or trio-exome analysis. We contacted the families and physicians of the six individuals to collect phenotypic information, performed in vitro analyses of the identified PRKAR1B-variants, and investigated PRKAR1B expression during embryonic development. Read More

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ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H-ATPases is essential for brain development in humans and mice.

Nat Commun 2021 04 8;12(1):2107. Epub 2021 Apr 8.

Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Vacuolar H-ATPases (V-ATPases) transport protons across cellular membranes to acidify various organelles. ATP6V0A1 encodes the a1-subunit of the V0 domain of V-ATPases, which is strongly expressed in neurons. However, its role in brain development is unknown. Read More

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Long-term survival of an ovarian cancer patient harboring a RAD51C missense mutation.

Cold Spring Harb Mol Case Stud 2021 Apr 8;7(2). Epub 2021 Apr 8.

Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.

Mutations in homologous recombination (HR) genes predispose to cancer but also sensitize to chemotherapeutics. Although therapy can initially be effective, cancers frequently cease responding, leading to recurrence and poor prognosis. Here we identify a germline mutation in , a critical HR factor and known tumor suppressor, in an ovarian cancer patient with exceptionally long, progression-free survival. Read More

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De Novo mutation of FOXF1 causes alveolar capillary dysplasia with misalignment of pulmonary veins: A case report.

Medicine (Baltimore) 2021 Apr;100(14):e25375

Department of Cardiology, Kunming Children's Hospital, Kunming, Yunnan.

Rationale: Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is a rare congenital malformation in neonates that results in severe respiratory distress and pulmonary hypertension. ACD/MPV is caused by mutations in the FOXF1 gene. Herein, a new case of a girl with ACD/MPV carrying a novel pathogenic variant of FOXF1 was reported. Read More

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Tay-Sachs Disease: Two Novel Rare HEXA Mutations from Pakistan and Morocco.

Klin Padiatr 2021 Apr 8. Epub 2021 Apr 8.

Institute of Biochemistry and Biotechnology, Pir Mehar Ali Shah Arid Agriculture University, Rawalpindi, Pakistan.

Background: Tay-Sachs disease (TSD) is a rare autosomalrecessive genetic disorder characterized by progressive destruction of nerve cells in the brain and spinal cord. It is caused by genetic variations in the HEXA gene leading to a deficiency of β hexosaminidase A (HEXA) isoenzyme activity. This study aimed to identify causative gene variants in 3 unrelated consanguineous families presented with TSD from Pakistan and Morocco. Read More

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Genetic variants of flavin-containing monooxygenase 3 (FMO3) in Japanese subjects identified by phenotyping for trimethylaminuria and found in a database of genome resources.

Drug Metab Pharmacokinet 2021 Feb 25;38:100387. Epub 2021 Feb 25.

Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Tokyo, Japan. Electronic address:

The oxygenation of food-derived trimethylamine to its N-oxide is a representative reaction mediated by human flavin-containing monooxygenase 3 (FMO3). Impaired FMO3 enzymatic activity is associated with trimethylaminuria (accumulation of substrate), whereas trimethylamine N-oxide (metabolite) is associated with arteriosclerosis. We previously reported FMO3 single-nucleotide and/or haplotype variants with low FMO3 metabolic capacity using urinary phenotyping and the whole-genome sequencing of Japanese populations. Read More

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February 2021

Functional variability of rhesus macaque (Macaca mulatta) NAT2 gene for drug-metabolising arylamine N-acetyltransferase 2.

Biochem Pharmacol 2021 Apr 5:114545. Epub 2021 Apr 5.

Democritus University of Thrace, Department of Molecular Biology and Genetics, Alexandroupolis, Greece. Electronic address:

Human NAT2 is a polymorphic pharmacogene encoding for N-acetyltransferase 2, a hepatic enzyme active towards arylamine and arylhydrazine drugs, including the anti-tubercular antibiotic isoniazid. The isoenzyme also modulates susceptibility to chemical carcinogenesis, particularly of the bladder. Human NAT2 represents an ideal model for anthropological investigations into the demographic adaptation of worldwide populations to their xenobiotic environment. Read More

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The role of a mechanistic host in maintaining arctic rabies variant distributions: Assessment of functional genetic diversity in Alaskan red fox (Vulpes vulpes).

PLoS One 2021 8;16(4):e0249176. Epub 2021 Apr 8.

Environmental and Life Sciences Graduate Program, Trent University, Peterborough, Ontario, Canada.

Populations are exposed to different types and strains of pathogens across heterogeneous landscapes, where local interactions between host and pathogen may present reciprocal selective forces leading to correlated patterns of spatial genetic structure. Understanding these coevolutionary patterns provides insight into mechanisms of disease spread and maintenance. Arctic rabies (AR) is a lethal disease with viral variants that occupy distinct geographic distributions across North America and Europe. Read More

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Genomic characterization of small cell carcinomas of the uterine cervix.

Mol Oncol 2021 Apr 8. Epub 2021 Apr 8.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Small cell carcinoma (SCC) of the uterine cervix is a rare and aggressive form of neuroendocrine carcinoma, which resembles small cell lung cancer (SCLC) in its histology and poor survival rate. Here we sought to define the genetic underpinning of SCCs of the uterine cervix and compare their mutational profiles with those of human papillomavirus (HPV)-positive head and neck squamous cell carcinomas, HPV-positive cervical carcinomas and SCLCs using publicly available data. Using a combination of whole-exome and targeted massively parallel sequencing, we found that the nine uterine cervix SCCs, which were HPV18-positive (n=8) or HPV16-positive (n=1), harbored a low mutation burden, few copy number alterations and other than TP53 in two cases no recurrently mutated genes. Read More

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Mutation-specific non-canonical pathway of PTEN as a distinct therapeutic target for glioblastoma.

Cell Death Dis 2021 Apr 7;12(4):374. Epub 2021 Apr 7.

Department of Neurosurgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.

PTEN is one of the most frequently altered tumor suppressor genes in malignant tumors. The dominant-negative effect of PTEN alteration suggests that the aberrant function of PTEN mutation might be more disastrous than deletion, the most frequent genomic event in glioblastoma (GBM). This study aimed to understand the functional properties of various PTEN missense mutations and to investigate their clinical relevance. Read More

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Identification of chemical and pharmacological chaperones for correction of trafficking- deficient mutant CNGA3 channels.

Mol Pharmacol 2021 Apr 7. Epub 2021 Apr 7.

Institute for Ophthalmic Research, Molecular Genetics Laboratory, Germany

Trafficking deficiency caused by missense mutations is a well-known phenomenon occurring for mutant, misfolded proteins. Typically, the misfolded protein is retained by the protein quality control system and degraded by the endoplasmic reticulum-associated protein degradation pathway and thus does not reach its destination although residual function of the protein may be preserved. Chemical and pharmacological chaperones can improve the targeting of trafficking-deficient proteins and thus may be promising candidates for therapeutic applications. Read More

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Massive parallel sequencing in a family with rectal cancer.

Hered Cancer Clin Pract 2021 Apr 7;19(1):23. Epub 2021 Apr 7.

Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Stockholm, Sweden.

Background: We have previously reported a family with a suspected autosomal dominant rectal and gastric cancer syndrome without any obvious causative genetic variant. Here, we focused the study on a potentially isolated rectal cancer syndrome in this family.

Methods: We included seven family members (six obligate carriers). Read More

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Clinical and genetic characteristics of hypophosphatasia in Chinese children.

Orphanet J Rare Dis 2021 Apr 7;16(1):159. Epub 2021 Apr 7.

Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.

Background: Hypophosphatasia (HPP) is a rare inherited disorder, which is caused by loss-of-function mutations in the ALPL gene. HPP is a heterogeneous disease that has a wide spectrum of phenotypes. Few studies were carried out in the Chinese population with HPP, especially in children. Read More

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A novel missense mutation of CRYBA1 in a northern Chinese family with inherited coronary cataract with blue punctate opacities.

Eur J Ophthalmol 2021 Apr 7:11206721211008355. Epub 2021 Apr 7.

Department of Ophthalmology, Linyi People's Hospital, Linyi, China.

Purpose: To demonstrate the underlying genetic defect that contribute to inherited cataract in a northern Chinese pedigree.

Methods: The study recruited a family pedigree with a diagnosis of bilateral coronary cataract with blue punctate opacities. Fourteen family members and 100 healthy volunteers were enrolled. Read More

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Long-read sequencing identified a novel nonsense and a de novo missense of PPA2 in trans in a Chinese patient with autosomal recessive infantile sudden cardiac failure.

Clin Chim Acta 2021 Apr 4. Epub 2021 Apr 4.

Department of Cardiology, Children's Hospital of Soochow University, 92 Zhongnan Street, Suzhou Industrial Park, Suzhou 215025, Jiangsu, China. Electronic address:

Background And Aims: Biallelic missense variants in PPA2 gene cause infantile sudden cardiac failure (SCFI; OMIM #617222) characterized by sudden cardiac failure, sudden cardiac death in infants. Here, we present an unusual survivor with one inherited plus one de novo variant in PPA2. Since next-generation sequencing (NGS) fails to resolve variant phasing, which require long-read sequencing to clarify the diagnosis. Read More

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Novel Mutations of the TYMP Gene in Mitochondrial Neurogastrointestinal Encephalomyopathy: Case Series and Literature Review.

J Mol Neurosci 2021 Apr 6. Epub 2021 Apr 6.

School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a multi-system disorder caused by several homozygous or compound heterozygous mutations, mostly in the nuclear gene of TYMP. Our current knowledge on the underlying pathology of the disease is derived through the study of about 200 cases of different ethnicities. Clinical presentations include severe cachexia, weakness, ptosis, diplopia, abdominal cramps or digestive tract disorders, hearing impairment, and paresthesia. Read More

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