108,599 results match your criteria heterozygous state

The phosphatase PRL-3 affects intestinal homeostasis by altering the crypt cell composition.

J Mol Med (Berl) 2021 Jun 15. Epub 2021 Jun 15.

European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.

Expression of the phosphatase of regenerating liver-3 (PRL-3) is known to promote tumor growth in gastrointestinal adenocarcinomas, and the incidence of tumor formation upon inflammatory events correlates with PRL-3 levels in mouse models. These carcinomas and their onset are associated with the impairment of intestinal cell homeostasis, which is regulated by a balanced number of Paneth cells and Lgr5 expressing intestinal stem cells (Lgr5+ ISCs). Nevertheless, the consequences of PRL-3 overexpression on cellular homeostasis and ISC fitness in vivo are unexplored. Read More

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Genome analysis of Candida subhashii reveals its hybrid nature and dual mitochondrial genome conformations.

DNA Res 2021 Jun 15. Epub 2021 Jun 15.

Life Sciences Department, Barcelona Supercomputing Center (BSC). Jordi Girona, 29. 08034, Barcelona, Spain.

Candida subhashii belongs to the CUG-Ser clade, a group of phylogenetically closely related yeast species that includes some human opportunistic pathogens, such as Candida albicans. Despite being present in the environment, C. subhashii was initially described as the causative agent of a case of peritonitis. Read More

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Phenotypic spectrum and mechanism analysis of Schaff Yang syndrome: A case report on new mutation of MAGEL2 gene.

Medicine (Baltimore) 2021 Jun;100(24):e26309

Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong First Medical University.

Rationale: The Schaaf-Yang syndrome (SYS) is an autosomal dominant multi-system genetic disease caused by melanoma antigen L2 (MAGEL2) gene mutations imprinted by mothers and expressed by fathers on the 15q11-15q13 chromosomes in the critical region of Prader-Willi. MAGEL2 is a single exon gene and one of the protein-coding genes of the Prader-Willi domain. MAGEL2 is a matrilineal imprinted gene (i. Read More

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Lymphedema complicated by protein-losing enteropathy with a 22q13.3 deletion and the potential role of CELSR1: A case report.

Medicine (Baltimore) 2021 Jun;100(24):e26307

Department of Lymphatic Surgery, Beijing Shijitan Hospital, Capital Medical University.

Introduction: 22q13.3 deletion syndrome is a well-known syndrome characterized by typical clinical findings including neonatal hypotonia, absent or severely delayed speech, intellectual disability, and other various features, and detection of a heterozygous deletion of chromosome 22q13.3 with the involvement of at least part of SHANK3. Read More

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CAV1 rs7804372 (T29107A) polymorphism might be a potential risk for digestive cancers: A protocol for systematic review and meta analysis.

Medicine (Baltimore) 2021 Jun;100(24):e26186

Department of Medical Technology, Jiangsu College of Nursing, Huai an, Jiangsu, China.

Background: Caveolin-1 (CAV1) is an essential structural component of caveolae, regulates cellular processes through complex cellular signaling pathways, and influences tumorigenicity. However, the role of the CAV1 (rs7804372) polymorphism in digestive cancers remains inconclusive. The meta-analysis was performed to evaluate the effect of CAV1 polymorphism on digestive cancer susceptibility and to provide a basis for precise treatment. Read More

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Novel DIO1 gene mutation acting as phenotype modifier for novel compound heterozygous TPO gene mutations causing congenital hypothyroidism.

Thyroid 2021 Jun 15. Epub 2021 Jun 15.

University of Miami School of Medicine, 12235, Medicine, 1120 NW 14th St, Suite 310F, Miami, Florida, United States, 33136-1015;

A family with congenital hypothyroidism was identified with 2 novel deleterious compound heterozygous thyroid peroxidase (TPO) mutations (c.962C>A, and c.1577C>T). Read More

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X-chromosome inactivation patterns in females with Fabry disease examined by both ultra-deep RNA sequencing and methylation-dependent assay.

Clin Exp Nephrol 2021 Jun 14. Epub 2021 Jun 14.

Department of Nephrology, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: Fabry disease is an X-linked inherited lysosomal storage disorder caused by mutations in the gene encoding α-galactosidase A. Males are usually severely affected, while females have a wide range of disease severity. This variability has been assumed to be derived from organ-dependent skewed X-chromosome inactivation (XCI) patterns in each female patient. Read More

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Parkinson's disease-associated VPS35 mutant reduces mitochondrial membrane potential and impairs PINK1/Parkin-mediated mitophagy.

Transl Neurodegener 2021 Jun 15;10(1):19. Epub 2021 Jun 15.

Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Background: Mitochondrial dysfunction plays a prominent role in the pathogenesis of Parkinson's disease (PD), and several genes linked to familial PD, including PINK1 (encoding PTEN-induced putative kinase 1 [PINK1]) and PARK2 (encoding the E3 ubiquitin ligase Parkin), are directly involved in processes such as mitophagy that maintain mitochondrial health. The dominant p.D620N variant of vacuolar protein sorting 35 ortholog (VPS35) gene is also associated with familial PD but has not been functionally connected to PINK1 and PARK2. Read More

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Novel DNAH17 mutations associated with fertilization failures after ICSI.

Gynecol Endocrinol 2021 Jun 14:1-3. Epub 2021 Jun 14.

The ART Center, Northwest Women and Children's Hospital, Xi'an, China.

Objective: Fertilization is a key event in human reproduction. The male genetic factors associated with total fertilization failure (TFF) are largely unknown. To date, only mutations in PLCZ1 have been reported as male factors that result in human fertilization failure. Read More

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Aberrant splicing and transcriptional activity of TPP1 result in CLN2-like disorder.

Eur J Med Genet 2021 Jun 11:104259. Epub 2021 Jun 11.

Murdoch Children's Research Institute, The Royal Children's Hospital, Victoria, Australia; Institute for Molecular Bioscience, The University of Queensland, Queensland, Australia. Electronic address:

RNA sequencing (RNAseq) is emerging as a complementary tool to DNA sequencing, providing utility in diagnosis for disorders such as neuronal ceroid lipofuscinosis CLN2 disease. We describe an individual with a presentation suggestive of an attenuated CLN2 phenotype, including a history of regression, recent-onset microcephaly and spasticity from age five years. Exome sequencing revealed two variants inherited in trans in TPP1, NM_000391. Read More

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ALA-PDT successfully treated multiple cSCC in situ and AK in a patient with Epidermodysplasia verruciformis.

Photodiagnosis Photodyn Ther 2021 Jun 11:102395. Epub 2021 Jun 11.

Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address:

5-aminolaevulinic acid photodynamic therapy (ALA-PDT) has emerged as a non-invasive treatment modality for premalignant and malignant skin lesions. It has the advantage of better tolerance and providing better cosmetic outcomes than conventional treatment methods. Herein, we report a patient who suffered from multiple cutaneous squamous cell carcinoma (cSCC) in situ and actinic keratosis (AK) scattered in the body's sun-exposed areas, which had led him to undergo multiple surgical resections since the age of 16. Read More

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Loss of cGMP-dependent protein kinase II alters ultrasonic vocalizations in mice, a model for speech impairment in human microdeletion 4q21 syndrome.

Neurosci Lett 2021 Jun 11:136048. Epub 2021 Jun 11.

Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, 80523, USA; Molecular, Cellular and Integrative Neurosciences Program, Colorado State University, Fort Collins, CO, 80523, USA. Electronic address:

Chromosome 4q21 microdeletion leads to a human syndrome that exhibits restricted growth, facial dysmorphisms, mental retardation, and absent or delayed speech. One of the key genes in the affected region of the chromosome is PRKG2, which encodes cGMP-dependent protein kinase II (cGKII). Mice lacking cGKII exhibit restricted growth and deficits in learning and memory, as seen in the human syndrome. Read More

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IGF1 Haploinsufficiency in Children with Short Stature: A Case Series.

Eur J Endocrinol 2021 Jun 1. Epub 2021 Jun 1.

D Beckers, Pediatric Endocrinology, Université Catholique de Louvain, CHU UCL Namur, Yvoir, Belgium.

Context: Short stature in children is a common reason for referral to pediatric endocrinologists. The underlying cause of short stature remains unclear in many cases and patients often receive unsatisfactory, descriptive diagnoses. While textbooks underline the rarity of genetic causes of growth hormone (GH) insensitivity and the severity of its associated growth failure, increased genetic testing in patients with short stature of unclear origin has revealed gene defects in the GH/ insulin-like growth factor (IGF-I) axis associated with milder phenotypes. Read More

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Role of an 1930_1931del TC gene mutation in a temporal cluster of macrocyclic lactone-induced neurologic toxicosis in cats associated with products labeled for companion animal use.

J Am Vet Med Assoc 2021 Jul;259(1):72-76

Objective: To determine whether 1930_1931del TC predisposed cats to macrocyclic-lactone toxicosis and the frequency of the 1930_1931del TC gene mutation in banked feline DNA samples.

Sample: DNA samples from 5 cats presented for neurologic clinical signs presumed to be caused by exposure to macrocyclic lactones and 1,006 banked feline DNA samples.

Procedures: The medical history pertaining to 5 cats was obtained from veterinarians who examined, treated, or performed necropsies on them. Read More

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R1441G but not G2019S mutation enhances LRRK2 mediated Rab10 phosphorylation in human peripheral blood neutrophils.

Acta Neuropathol 2021 Jun 14. Epub 2021 Jun 14.

Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, DD1 5EH, UK.

Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. All pathogenic LRRK2 mutations reside within the two catalytic domains of LRRK2-either in its kinase domain (e.g. Read More

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Mild Idiopathic Infantile Hypercalcemia - Part 1: Biochemical and Genetic Findings.

J Clin Endocrinol Metab 2021 Jun 14. Epub 2021 Jun 14.

Division of Endocrinology and Diabetes and Center for Bone Health, Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States.

Context: Idiopathic Infantile Hypercalcemia (IIH), an uncommon disorder characterized by elevated serum concentrations of 1,25(OH)2D and low PTH levels, may present with mild to severe hypercalcemia during the first months of life. Biallelic variants in the CYP24A1 or SLC34A1 genes are associated with severe IIH. Little is known about milder forms. Read More

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North Carolina Macular Dystrophy: Phenotypic Variability and Computational Analysis of Disease-Associated Noncoding Variants.

Invest Ophthalmol Vis Sci 2021 Jun;62(7):16

Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.

Purpose: North Carolina macular dystrophy (NCMD) is an autosomal dominant, congenital disorder affecting the central retina. Here, we report clinical and genetic findings in three families segregating NCMD and use epigenomic datasets from human tissues to gain insights into the effect of NCMD-implicated variants.

Methods: Clinical assessment and genetic testing were performed. Read More

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DIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease.

JAMA Neurol 2021 Jun 14. Epub 2021 Jun 14.

Yale Center for Genome Analysis, West Haven, Connecticut.

Importance: Moyamoya disease (MMD), a progressive vasculopathy leading to narrowing and ultimate occlusion of the intracranial internal carotid arteries, is a cause of childhood stroke. The cause of MMD is poorly understood, but genetic factors play a role. Several familial forms of MMD have been identified, but the cause of most cases remains elusive, especially among non-East Asian individuals. Read More

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Identification of Two Novel Compound Heterozygous Mutations Underlying Wolcott-Rallison Syndrome in a Chinese Family.

Front Pediatr 2021 26;9:679646. Epub 2021 May 26.

Institutes of Biomedical Sciences, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China.

Wolcott-Rallison syndrome is a rare autosomal recessive inheritance disorder caused by the defectiveness of eukaryotic translation initiation factor 2 alpha kinase 3 (), which encodes the PKR-like endoplasmic reticulum kinase (PERK). Defect in results in a permanent diabetes in early infancy or newborn period, a tendency to develop skeletal fractures and other associated disorders such as severe liver and renal dysfunction, and central hypothyroidism. Two patients with Wolcott-Rallison syndrome-like manifestations in a Chinese family and family members were genetically analyzed to identify if any variations that occurred in , which may cause Wolcott-Rallison syndrome. Read More

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Four New Cases of SLC35A2-CDG With Novel Mutations and Clinical Features.

Front Genet 2021 27;12:658786. Epub 2021 May 27.

Department of Hepatology, Children's Hospital of Fudan University, Shanghai, China.

SLC35A2-CDG is a rare type of X-linked CDG with more than 60 reported cases. We retrospectively analyzed clinical phenotypes and genotypes of four cases of SLC35A2-CDG from four unrelated families of Han ethnicity in China. All patients had infantile onset epilepsies that were completely or partly resistant to multiple anti-epileptic medications or ketogenic diet. Read More

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Toward pharmacogenetic SLCO1B1-guided dosing of methotrexate in arthritis using a murine Slco1b2 knockout model.

Clin Transl Sci 2021 Jun 13. Epub 2021 Jun 13.

Division of Research in Patient Services, Cincinnati Children's Hospital Medical Center, Cincinnati.

Low-dose methotrexate (MTX) is a first-line therapy for the treatment of arthritis. However, there is considerable inter-individual variability in MTX exposure following standard dosing. Polymorphisms in SLCO1B1 significantly effect MTX clearance, altering therapeutic response. Read More

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Early diagnosis of lateral meningocele syndrome in an infant without neurological symptoms based on genomic analysis.

Childs Nerv Syst 2021 Jun 13. Epub 2021 Jun 13.

Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.

Lateral meningocele syndrome is characterized by multiple lateral meningoceles with a distinctive craniofacial appearance, hyperextensibility of the skin, and hypermobility of the joints. The syndrome is caused by heterozygous truncating variants in the last exon, exon 33, of the NOTCH3 gene. Here, we present a 2-year-old girl for whom an early genomic analysis allowed us to recognize the presence of lateral meningoceles and to begin early monitoring of her condition for possible neurological complications. Read More

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Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay without Spasticity.

Intern Med 2021 Jun 12. Epub 2021 Jun 12.

Department of Neurology, National Hospital Organization Niigata National Hospital, Japan.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare progressive neurodegenerative disease caused by either homozygous or compound heterozygous mutations in the SACS gene. The original ARSACS cases found in Quebec showed very homogenous phenotypes characterized by cerebellar ataxia, spasticity, and polyneuropathy. However, many cases with atypical phenotypes have been found in other regions and ethnic groups. Read More

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Whole-body R2∗ mapping to quantify tissue iron in iron storage organs: reference values and a genotype.

Clin Radiol 2021 Jun 10. Epub 2021 Jun 10.

Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany; Institute and Policlinic for Diagnostic and Interventional Radiology, University Hospital, Carl Gustav Carus University, TU Dresden, Dresden, Germany. Electronic address:

Aim: To define reference values for the transverse relaxation rate (R2∗) in iron storage organs and to investigate the role of human haemochromatosis protein (HFE) genotype on iron storage.

Materials And Methods: Whole-body magnetic resonance imaging (MRI) including a five-echo gradient-echo sequence was performed in 483 volunteers (269 men, mean age 59.3 ± 12. Read More

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A novel homozygous missense variant in the NAXE gene in an Iranian family with progressive encephalopathy with brain edema and leukoencephalopathy.

Acta Neurol Belg 2021 Jun 13. Epub 2021 Jun 13.

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Jalah-Al Ahmad Hwy, 14117-1316, Tehran, Iran.

Homozygous or compound heterozygous mutations in the NAD(P)HX epimerase (NAXE) gene, cause early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy 1. This disorder is characterized by psychomotor regression, hypotonia, ataxia, respiratory insufficiency, tetraparesis, and seizures, leading to coma and death in early childhood. In this study, whole-exome sequencing was used to identify the pathogenic variant, followed by confirmation of identified variant in the proband and segregation analysis in the family by Sanger sequencing. Read More

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A Crohn's disease-associated IL2RA enhancer variant determines the balance of T cell immunity by regulating responsiveness to IL-2 signaling.

J Crohns Colitis 2021 Jun 12. Epub 2021 Jun 12.

School of Immunology and Microbial Sciences, King's College London, Great Maze Pond, London SE1 9RT, UK.

Background And Aims: Differential responsiveness to interleukin (IL)-2 between effector CD4¬+ T cells (Teff) and regulatory T cells (Treg) is a fundamental mechanism of immunoregulation. The single nucleotide polymorphism rs61839660, located within IL2RA (CD25), has been associated with the development of Crohn's disease. We sought to identify the T cell immune phenotype of IBD patients who carry this SNP. Read More

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Epigenetic regulation of TXNIP-mediated oxidative stress and NLRP3 inflammasome activation contributes to SAHH inhibition-aggravated diabetic nephropathy.

Redox Biol 2021 Jun 5;45:102033. Epub 2021 Jun 5.

Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China. Electronic address:

S-adenosylhomocysteine (SAH) is hydrolyzed by SAH hydrolase (SAHH) to homocysteine and adenosine. Increased plasma SAH levels were associated with disturbed renal function in patients with diabetes. However, the role and mechanism of SAHH in diabetic nephropathy is still unknown. Read More

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A patient with POLA1 splice variant expands the yet evolving phenotype of Van Esch O'Driscoll syndrome.

Eur J Med Genet 2021 Jun 10:104261. Epub 2021 Jun 10.

Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), New Delhi, India, 110029. Electronic address:

Van Esch-O'Driscoll syndrome (VEODS) is a rare cause of syndromic X-linked intellectual disability characterised by short stature, microcephaly, variable degree of intellectual disability, and hypogonadotropic hypogonadism. To date, heterozygous hypomorphic variants in the gene encoding the DNA Polymerase α subunit, POLA1, have previously been observed in nine patients from five unrelated families with VEODS. We report a three-year-old child with VEODS having borderline intellectual disability due to a novel splice site variant causing exon 6 skipping and reduced POLA1 expression. Read More

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Curating the gnomAD Database: Report of Novel Variants in the Thyrogobulin Gene using in silico Bioinformatics Algorithms.

Mol Cell Endocrinol 2021 Jun 10:111359. Epub 2021 Jun 10.

Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética/Cátedra de Genética. Buenos Aires, Argentina; CONICET-Universidad de Buenos Aires. Instituto de Inmunología, Genética y Metabolismo (INIGEM). Buenos Aires, Argentina. Electronic address:

Thyroglobulin (TG) is a large glycosylated protein of 2,767 amino acids, secreted by the thyrocytes into the follicular lumen. It plays an essential role in the process of thyroid hormone synthesis. TG gene variants lead to permanent congenital hypothyroidism. Read More

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Advances in familial hypercholesterolaemia in children.

Lancet Child Adolesc Health 2021 Jun 10. Epub 2021 Jun 10.

Department of Pediatrics, Amsterdam University Medical Center, Amsterdam, Netherlands. Electronic address:

Familial hypercholesterolaemia is a common, dominantly inherited disease that results in high concentrations of low-density lipoprotein cholesterol and in premature cardiovascular disease. To prevent cardiovascular disease and premature mortality, patients with the condition need to be identified and to start treatment early in life. In this Review, we discuss the treatment of heterozygous and homozygous familial hypercholesterolaemia in children, including lifestyle modifications, current pharmacological treatment options, and promising novel lipid-lowering treatments. Read More

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