21,550 results match your criteria identified missense

Genomic variation in captive deer mouse (Peromyscus maniculatus) populations.

BMC Genomics 2021 Sep 14;22(1):662. Epub 2021 Sep 14.

Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, USA.

Background: Deer mice (genus Peromyscus) are the most common rodents in North America. Despite the availability of reference genomes for some species, a comprehensive database of polymorphisms, especially in those maintained as living stocks and distributed to academic investigators, is missing. In the present study we surveyed two populations of P. Read More

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September 2021

Genetic predisposition to tinnitus in the UK Biobank population.

Sci Rep 2021 Sep 13;11(1):18150. Epub 2021 Sep 13.

Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA.

Tinnitus, the phantom perception of noise originating from the inner ear, has been reported by 15% of the world's population, with many patients reporting major deficits to cognition and mood. However, both objective diagnostic tools and targeted therapeutic strategies have yet to be established. To better understand the underlying genes that may preclude tinnitus, we performed a genome-wide association study of the UK Biobank's 49,960 whole exome sequencing participants to identify any loci strongly associated with tinnitus. Read More

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September 2021

Topology of phosphatidylserine synthase 1 in the endoplasmic reticulum membrane.

Protein Sci 2021 Sep 13. Epub 2021 Sep 13.

Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka, Japan.

Phosphatidylserine (PS) synthase 1 (PSS1) of mammalian cells is a multiple membrane-spanning protein of the endoplasmic reticulum (ER) and regulated by inhibition with the product PS. Alanine-scanning mutagenesis of PSS1 has revealed eight amino acid residues as those crucial for its activity and six as those important for its regulation. Furthermore, three missense mutations in the human PSS1 gene, which lead to regulatory dysfunctions of PSS1 and are causative of Lenz-Majewski syndrome, have been identified. Read More

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September 2021

Heterozygous variants in ZBTB7A cause a neurodevelopmental disorder associated with symptomatic overgrowth of pharyngeal lymphoid tissue, macrocephaly, and elevated fetal hemoglobin.

Am J Med Genet A 2021 Sep 13. Epub 2021 Sep 13.

Department of Medical Genetics, St. Olavs University Hospital, Trondheim, Norway.

By clinical whole exome sequencing, we identified 12 individuals with ages 3 to 37 years, including three individuals from the same family, with a consistent phenotype of intellectual disability (ID), macrocephaly, and overgrowth of adenoid tissue. All 12 individuals harbored a rare heterozygous variant in ZBTB7A which encodes the transcription factor Zinc finger and BTB-domain containing protein 7A, known to play a role in lympho- and hematopoiesis. ID was generally mild. Read More

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September 2021

Family History is Important to Identify Patients with Monogenic Causes of Adult-Onset Chronic Kidney Disease.

Nephron 2021 Aug 30:1-9. Epub 2021 Aug 30.

Department of Clinical Genetics, Lillebaelt Hospital, University Hospital of Southern Denmark, Vejle, Denmark.

Monogenic causes of chronic kidney disease (CKD) are more prevalent in adults than previously thought, as causative gene variants are found in almost 10% of unselected patients with CKD. Even so, genetic testing in patients with adult-onset CKD is uncommon in clinical practice and the optimal criteria for patient selection remain unclear. A family history of kidney disease emerges as one marker associated with a high diagnostic yield of genetic testing. Read More

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A Patient with Kabuki Syndrome Mutation Presenting with Very Severe Aplastic Anemia.

Acta Haematol 2021 Sep 3:1-8. Epub 2021 Sep 3.

Department of Hematology/Oncology, Wakayama Medical University, Wakayama, Japan.

Kabuki syndrome (KS) is a rare congenital disorder commonly complicated by humoral immunodeficiency. Patients with KS present with mutation in the histone-lysine N-methyltransferase 2D (KMT2D) gene. Although various KMT2D mutations are often identified in lymphoma and leukemia, those encountered in aplastic anemia (AA) are limited. Read More

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September 2021

Clinicoradiographic and genetic features of cerebral small vessel disease indicate variability in mode of inheritance for monoallelic HTRA1 variants.

Mol Genet Genomic Med 2021 Sep 12:e1799. Epub 2021 Sep 12.

Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.

Background: Biallelic pathogenic variants in HTRA1 cause CARASIL. More recently, monoallelic variants have been associated with the autosomal dominant disorder CADASIL2 but not all carriers develop disease manifestations. We describe the clinicoradiologic and mutation spectrum of four new CADASIL2 individuals. Read More

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September 2021

X-linked adrenoleukodystrophy: phenotype-genotype correlation in hemizygous males and heterozygous females with ABCD1 mutations.

Neuro Endocrinol Lett 2021 Sep 10;42(5):359-367. Epub 2021 Sep 10.

Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General Faculty Hospital, Prague, Czech Republic.

Objectives: X-linked adrenoleukodystrophy (X-ALD) causes cerebral adrenoleukodystrophy (cALD), myelopathy and/or adrenal insufficiency in males, and myelopathy/peripheral neuropathy in females. These distinct phenotypes are scarcely linked to a specific mutations. The objective herein was to find a link between the phenotype with the genotype mutation, serum very long-chain fatty acids (VLCFA), and the diet with Lorenzo´s and GTO oils in hemizygous males and heterozygous females. Read More

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September 2021

De novo missense variants in FBXO11 alter its protein expression and subcellular localization.

Hum Mol Genet 2021 Sep 9. Epub 2021 Sep 9.

Research Centre for Medical Genetics, Moscow, 115522, Russia.

Recently, we and others identified de novo FBXO11 variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. Read More

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September 2021

Germline G212E Missense Variant: Combining Clinical, In Vitro and In Vivo Strategies to Unravel Disease Burden.

Cancers (Basel) 2021 Aug 28;13(17). Epub 2021 Aug 28.

Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.

E-cadherin, encoded by , is an essential molecule for epithelial homeostasis, whose loss or aberrant expression results in disturbed cell-cell adhesion, increased cell invasion and metastasis. Carriers of germline mutations have a high risk of developing diffuse gastric cancer and lobular breast cancer, associated with the cancer syndrome Hereditary Diffuse Gastric Cancer (HDGC). The ubiquitous availability of cancer panels has led to the identification of an increasing amount of "incidental" genetic variants that pose a serious clinical challenge. Read More

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Combined approaches identify known and novel genes associated with sheep litter size and non-seasonal breeding.

Anim Genet 2021 Sep 7. Epub 2021 Sep 7.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

Improvement of ewe reproduction is considerable by appropriately increasing litter size and sustaining non-seasonal breeding. However, their genetic makeups have not been entirely elucidated. Genome-wide analyses of 821 individuals were performed by combining three genomic approaches (genome-wide association study, XP-nSL, and runs of homozygosity). Read More

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September 2021

Distinct functional classes of PDGFRB pathogenic variants in primary familial brain calcification.

Hum Mol Genet 2021 Sep 7. Epub 2021 Sep 7.

De Duve Institute, Université catholique de Louvain, BE-1200, Brussels, Belgium.

Platelet-derived growth factor receptor beta (PDGFRB) is one of the genes associated with primary familial brain calcification (PFBC), an inherited neurological disease (OMIM:173410). Genetic analysis of patients and families revealed at least 13 PDGFRB heterozygous missense variants, including two novel ones described in the present report. Limited experimental data published on five of these variants had suggested that they decrease the receptor activity. Read More

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September 2021

Monogenic Epilepsies: Disease Mechanisms, Clinical Phenotypes, and Targeted Therapies.

Neurology 2021 Sep 7. Epub 2021 Sep 7.

Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.

A monogenic aetiology can be identified in up to 40% of people with severe epilepsy. To address earlier and more appropriate treatment strategies, clinicians are required to know the implications that specific genetic causes might have on pathophysiology, natural history, comorbidities and treatment choices. In this narrative review, we summarise concepts on the genetic epilepsies based on the underlying pathophysiological mechanisms and present the current knowledge on treatment options based on evidence provided by controlled trials or studies with lower classification of evidence. Read More

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September 2021

Biallelic variants of cause dose-dependent childhood-onset pulmonary arterial hypertension characterised by extreme morbidity and mortality.

J Med Genet 2021 Sep 7. Epub 2021 Sep 7.

Department of Pediatrics and Medicine, Columbia University Irving Medical Center, New York, New York, USA

Background: The molecular genetic basis of pulmonary arterial hypertension (PAH) is heterogeneous, with at least 26 genes displaying putative evidence for disease causality. Heterozygous variants in the gene were recently identified as a new cause of adult-onset PAH. However, the contribution of risk alleles to child-onset PAH remains largely unexplored. Read More

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September 2021

A missense variant rs2585405 in clock gene PER1 is associated with the increased risk of noise-induced hearing loss in a Chinese occupational population.

BMC Med Genomics 2021 Sep 8;14(1):221. Epub 2021 Sep 8.

Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 210000, Jiangsu, China.

Objective: To investigate the potential association of cochlear clock genes (CRY1, CRY2, PER1, and PER2), the DNF gene (brain-derived neurotrophic factor), and the NTF3 gene (neurotrophin3) with susceptivity to noise-induced hearing loss (NIHL) among Chinese noise-exposed workers.

Methods: A nested case-control study was performed with 2056 noise-exposed workers from a chemical fiber factory and an energy company who underwent occupational health examinations in 2019 as study subjects. Propensity score matching was conducted to screen cases and controls by matching sex, age, and the consumption of tobacco and alcohol. Read More

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September 2021

De novo mutation in COL2A1 leads to lethal foetal skeletal dysplasia.

Bone 2021 Sep 4:116169. Epub 2021 Sep 4.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China; Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. Electronic address:

Objective: Skeletal dysplasia caused by genetic mutations places a heavy burden on families and society. This study was performed to precise diagnosis of variants of unknown significance and to expand the genotypic spectrum of lethal skeletal dysplasia.

Methods: According to the ultrasonic phenotype of the proband and whole-exome sequencing results, variation sites or genes that may be related to the disease were screened out. Read More

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September 2021

RPE65-related retinal dystrophy: Mutational and phenotypic spectrum in 45 affected patients.

Exp Eye Res 2021 Sep 4:108761. Epub 2021 Sep 4.

Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital-Universidad Autónoma de Madrid (IIS-FJD, UAM), Centre for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain. Electronic address:

Introduction: Biallelic pathogenic RPE65 variants are related to a spectrum of clinically overlapping inherited retinal dystrophies (IRD). Most affected individuals progress to severe disease, with 50% of patients becoming legally blind by 20 years of age. Deeper knowledge of the mutational spectrum and the phenotype-genotype correlation in RPE65-related IRD is needed. Read More

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September 2021

Whole Exome Sequencing in Individuals with Idiopathic Clubfoot Reveals a Recurrent Filamin B (FLNB) Deletion.

Clin Orthop Relat Res 2021 Sep 6. Epub 2021 Sep 6.

Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA.

Background: Clubfoot, a congenital deformity that presents as a rigid, inward turning of the foot, affects approximately 1 in 1000 infants and occurs as an isolated birth defect in 80% of patients. Despite its high level of heritability, few causative genes have been identified, and mutations in known genes are only responsible for a small portion of clubfoot heritability.

Questions/purposes: (1) Are any rare gene variants enriched (that is, shared) in unrelated patients with isolated clubfoot? (2) Are there other rare variants in the identified gene (Filamin B) in these patients with clubfoot?

Methods: Whole-exome sequence data were generated from a discovery cohort of 183 unrelated probands with clubfoot and 2492 controls. Read More

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September 2021

Novel pathogenic OCRL mutations and genotype-phenotype analysis of Chinese children affected by oculocerebrorenal syndrome: two cases and a literature review.

BMC Med Genomics 2021 Sep 6;14(1):219. Epub 2021 Sep 6.

Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095, Jiefang Ave., Wuhan, 430030, People's Republic of China.

Background: Oculocerebrorenal syndrome of Lowe is a rare X-linked disorder characterized by congenital cataracts, mental retardation, and proximal tubulopathy. This condition is caused by a mutation of OCRL gene (located at chromosome Xq26.1), which encodes an inositol polyphosphate 5-phosphatase. Read More

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September 2021

Rare NRXN1 missense variants identified in autism interfered protein degradation and Drosophila sleeping.

J Psychiatr Res 2021 Sep 2;143:113-122. Epub 2021 Sep 2.

Center for Medical Genetics and Hunan Provincial Key Laboratory for Medical Genetics, School of Life Sciences, Central South University, Changsha, China; CAS Center for Excellence in Brain Science and Intelligences Technology (CEBSIT), Shanghai, China; Key Laboratory of Medical Information Research, Central South University, Changsha, Hunan, China. Electronic address:

NRXN1 is involved in synaptogenesis and have been implicated in Autism spectrum disorders. However, many rare inherited missense variants of NRXN1 have not been thoroughly evaluated. Here, functional analyses in vitro and in Drosophila of three NRXN1 missense mutations, Y282H, L893V, and I1135V identified in ASD patients in our previous study were performed. Read More

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September 2021

[Analysis of NF1 gene variants among thirteen patients with neurofibromatosis type 1].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Sep;38(9):829-832

Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan 450018, China.

Objective: To detect variants of NF1 gene among thirteen patients with neurofibromatosis type 1.

Methods: Genomic DNA was extracted from peripheral blood samples of the patients. High-throughput sequencing was employed to detect potential variants of the NF1 and NF2 genes. Read More

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September 2021

Molecular Screening of Gene Polymorphism in Primary Vesicoureteral Reflux Patients in Taif Governorate, KSA.

Pak J Biol Sci 2021 Jan;24(4):492-499

<b>Background and Objective:</b> Primary Nonsyndromic Vesicoureteral Reflux (PVUR) is a widespread genetic malformation and considered a prevalent Congenital Abnormality of the Kidney and Urinary Tract (CAKUT). Mutations in the <i>PAX2 </i>gene have been associated with abnormalities in the kidney extending from CAKUT to oncogenic processes. The present study analyzes the <i>PAX2</i> polymorphisms and their association with primary VUR in Saudi children patients from the Taif governorate. Read More

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January 2021

A Novel Gene Mutation Associated With Autosomal Dominant Retinal Degeneration.

Front Cell Dev Biol 2021 17;9:720782. Epub 2021 Aug 17.

Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, United States.

Despite major progress in the discovery of causative genes, many individuals and families with inherited retinal degenerations (IRDs) remain without a molecular diagnosis. We applied whole exome sequencing to identify the genetic cause in a family with an autosomal dominant IRD. Eye examinations were performed and affected patients were studied with electroretinography and kinetic and chromatic static perimetry. Read More

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Common calcium-sensing receptor (CASR) gene variants do not modify risk for chronic pancreatitis in a Hungarian cohort.

Pancreatology 2021 Aug 26. Epub 2021 Aug 26.

Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary. Electronic address:

The calcium-sensing receptor (CASR) is expressed in the pancreas where it might regulate calcium concentrations in pancreatic secretions. Two independent studies reported conflicting results claiming that commonly occurring missense variants of the CASR gene are risk factors for chronic pancreatitis (CP). Here, we attempted to replicate the association between CASR variants and CP. Read More

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Distal Renal Tubular Acidosis in an Iranian Patient with Hereditary Spherocytosis

Iran Biomed J 2021 09 1;25(5):359-67. Epub 2021 Sep 1.

Department of Cellular and Molecular Biology, Faculty of Science, North Tehran Branch of Islamic Azad University, Tehran, Iran.

Background: Hereditary spherocytosis (HS) and hereditary hereditary distal renal tubular acidosis (dRTA) are associated with mutations in the SLC4A1 gene encoding the anion exchanger 1. In this study, some patients with clinical evidence of congenital HS and renal symptoms were investigated.

Methods: Twelve patients with congenital HS and renal symptoms were recruited from Ali-Asghar Children’s Hospital (Tehran, Iran). Read More

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September 2021

Pulmonary fibrosis in dyskeratosis congenita: a case report with a PRISMA-compliant systematic review.

Ping Wang Zuojun Xu

BMC Pulm Med 2021 Sep 3;21(1):279. Epub 2021 Sep 3.

Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Dyskeratosis congenita (DC) is a rare genetic disorder of poor telomere maintenance. Pulmonary fibrosis (PF) related to DC is rarely reported.

Case Presentation: A 23-year-old student presented with a four-year history of progressive cough and exertional dyspnea. Read More

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September 2021

Trio exome sequencing identified a novel de novo WASF1 missense variant leading to recurrent site substitution in a Chinese patient with developmental delay, microcephaly, and early-onset seizures: A mutational hotspot p.Trp161 and literature review.

Clin Chim Acta 2021 Aug 31;523:10-18. Epub 2021 Aug 31.

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

Background: Neurodevelopmental disorder with absent language and variable seizures (NEDALVS, OMIM # 618707) is a newly described autosomal dominant condition caused by heterozygous de novo mutation in WASF1 gene. WASF1 is a key component of the WAVE regulatory complex (WRC) required for actin polymerization. So far, only 3 distinct truncating variants clustering at the WCA domain, 3 missense variants localized to the meander region and a copy number variant (CNV) of WASF1 have been identified among 11 NEDALVS cases previously reported. Read More

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PIEZO1-gene gain-of-function mutations with lower limb lymphedema onset in an adult: Clinical, scintigraphic, and noncontrast magnetic resonance lymphography findings.

Am J Med Genet A 2021 Sep 3. Epub 2021 Sep 3.

Service d'Hématologie Biologique, APHP, CHU Bicêtre, Le Kremlin-Bicêtre, France.

Primary lymphedema, a rare disease, has a genetic cause in ~40% of patients. Recently, loss-of-function mutations in PIEZO1, which encodes the mechanotransducer protein PIEZO1, were described as causing primary lymphedema, when gain-of-function PIEZO1 mutations were attributed to dehydrated hereditary stomatocytosis type-1 (DHS), a dominant red cell hemolytic disorder, with ~20% of patients having perinatal edema. Lymphedema was diagnosed in a 36-year-old man from a three-generation DHS family, with a PIEZO1-allele harboring 3 missense mutations in cis. Read More

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September 2021

Neuropathologic Findings in a Patient With Juvenile-Onset Levodopa Responsive Parkinsonism Due to Mutation.

Neurology 2021 Sep 2. Epub 2021 Sep 2.

Department of Neurology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil.

Objective: To describe the postmortem neuropathological findings of a patient with Kufor Rakeb Syndrome (KRS) due to ATP13A2 mutation. KRS is characterized by juvenile-onset, levodopa-responsive parkinsonism associated with pyramidal signs, supranuclear gaze palsy, and cognitive impairment.

Methods: Detailed neuropathological analysis of the brain. Read More

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September 2021