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Front Cell Dev Biol 2021 23;9:626821. Epub 2021 Mar 23.

Computational Biology Program, Ontario Institute for Cancer Research, Toronto, ON, Canada.

Deciphering the functional impact of genetic variation is required to understand phenotypic diversity and the molecular mechanisms of inherited disease and cancer. While millions of genetic variants are now mapped in genome sequencing projects, distinguishing functional variants remains a major challenge. Protein-coding variation can be interpreted using post-translational modification (PTM) sites that are core components of cellular signaling networks controlling molecular processes and pathways. Read More

Sci Rep 2021 Apr 8;11(1):7731. Epub 2021 Apr 8.

Department of Evolution, Ecology and Organismal Biology, Ohio State University, 318 W. 12th Avenue, Columbus, OH, 43210, USA.

Nutritional symbioses between bacteria and insects are prevalent and diverse, allowing insects to expand their feeding strategies and niches. A common consequence of long-term associations is a considerable reduction in symbiont genome size likely influenced by the radical shift in selective pressures as a result of the less variable environment within the host. While several of these cases can be found across distinct insect species, most examples provide a limited view of a single or few stages of the process of genome reduction. Read More

Acta Crystallogr D Struct Biol 2021 Apr 30;77(Pt 4):486-495. Epub 2021 Mar 30.

Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.

The canonical O-mannosylation pathway in humans is essential for the functional glycosylation of α-dystroglycan. Disruption of this post-translational modification pathway leads to congenital muscular dystrophies. The first committed step in the construction of a functional matriglycan structure involves the post-translational modification of α-dystroglycan. Read More

J Pediatr Endocrinol Metab 2021 Apr 6. Epub 2021 Apr 6.

Department of Neonatal Intensive Care Unit, Quanzhou Maternity and Children's Hospital, Quanzhou, Fujian Province, China.

Objectives: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid, amino acid and choline metabolism. Late-onset MADD is caused by mutations and is the most common lipid storage myopathy in China. However, few patients with MADD have been identified through newborn screening (NBS). Read More

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Mar;35(3):229-233;237

Department of Otorhinolaryngology Head and Neck Surgery，Union Hospital，Tongji Medical College，Huazhong University of Science and Technology，Wuhan，430022，China.

To identify the pathogenic gene mutation of two patients with non-syndromic deafness（NSHL）. Two patient with NSHL and their parents were selected in the research object. Each participant provided 3-5 mL of peripheral venous blood, which was used to establish a DNA library. Read More

J Steroid Biochem Mol Biol 2021 Mar 27:105882. Epub 2021 Mar 27.

Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, No.300, Guangzhou Road, Nanjing, Jiangsu, 210029, China. Electronic address:

Steroid 11β-hydroxylase deficiency (11β-OHD), which is caused by mutations of the CYP11B1 gene, is the second leading cause of congenital adrenal hyperplasia (CAH), an autosomal recessive inherited disorder. Here, we report a case of classic 11β-OHD in a Chinese boy characterized by hypertension, penile enlargement, skin pigmentation, and acne. Molecular analysis of CYP11B1 revealed that the patient was compound heterozygous for a c. Read More

Nat Metab 2021 03 18;3(3):394-409. Epub 2021 Mar 18.

Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia.

Both obesity and sarcopenia are frequently associated in ageing, and together may promote the progression of related conditions such as diabetes and frailty. However, little is known about the pathophysiological mechanisms underpinning this association. Here we show that systemic alanine metabolism is linked to glycaemic control. Read More

Methods Mol Biol 2021 ;2280:45-54

Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, University of Calabria, Arcavacata di Rende, Italy.

Riboflavin is essential for cell viability. The biologically active forms of riboflavin, FMN and FAD, participate in many biochemical redox reactions including the metabolism of carbohydrates, amino acids, and lipids. Differently from bacteria, fungi, and plants which synthesize riboflavin, higher organisms have lost the ability to synthesize the vitamin and must absorb it from food and intestinal microflora production. Read More

Gastroenterol Rep (Oxf) 2021 Jan 15;9(1):38-48. Epub 2021 Jan 15.

Department of Pediatrics, Adolescent and Internal Medicine, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, MI, USA.

Background: Medical literature on the prevalence of genetic liver disease is lacking. In this study, we investigated the in-hospital healthcare and economic burden from genetic causes of non-alcoholic chronic liver disease (NACLD) and non-alcoholic liver cirrhosis (NALC) in the USA.

Methods: Data were abstracted from the National Inpatient Sample database between 2002 and 2014 using ICD9 codes for patients discharged with NACLD and NALC secondary to genetic diseases including alpha-1 antitrypsin deficiency (A1ATd), cystic fibrosis (CF), Wilson disease (WD), hereditary hemochromatosis (HHC), glycogen storage disease, and disorders of aromatic amino-acid metabolism (DAAAM). Read More

Mol Genet Metab 2021 Mar 13. Epub 2021 Mar 13.

Neurology Unit, St Bassiano Hospital, Bassano del Grappa, Italy.

Objective: Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare inherited autosomal recessive disorder of biogenic amine metabolism. Diagnosis requires analysis of neurotransmitter metabolites in cerebrospinal fluid, AADC enzyme activity analysis, or molecular analysis of the DDC gene. 3-O-methyldopa (3-OMD) is a key screening biomarker for AADC deficiency. Read More

Brain 2021 Mar 17. Epub 2021 Mar 17.

Developmental Neurosciences, GOS Institute of Child Health, University College London, London, UK.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a complex inherited neurological disorder of monoamine synthesis which results in dopamine and serotonin deficiency. The majority of affected individuals have variable, though often severe cognitive and motor delay, with a complex movement disorder and high risk of premature mortality. For most, standard pharmacological treatment provides only limited clinical benefit. Read More

JIMD Rep 2021 Mar 16;58(1):12-20. Epub 2020 Nov 16.

Department of Paediatric Neurology Cork University Hospital Cork Republic of Ireland.

A 4-year-old girl was referred for reassessment of dyskinetic cerebral palsy. Initial investigations in her country of birth, India, had not yielded a diagnosis. MRI brain in infancy revealed bilateral putamen hyperintensity. Read More

Theor Appl Genet 2021 Mar 16. Epub 2021 Mar 16.

National Key Laboratory of Crop Genetic Improvement, National Centre of Rapeseed Improvement, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

Key Message: A mitochondria-localized pentatricopeptide repeat protein was identified by positional cloning and transferred into the hau CMS line, where it successfully restored fertility Cytoplasmic male sterility (CMS) is a maternally inherited trait that can be controlled by restorer-of-fertility (Rf) genes present in the nucleus. The hau CMS was identified as a new form of CMS associated with the mitochondrial transcript orf288; however, a lack of a restorer gene has limited its utilization in Brassica crops. Here, the combination of Brassica 60 K array with bulk segregant analysis and map-based cloning was used to delimit the Rfh locus to an 82. Read More

Orphanet J Rare Dis 2021 Mar 10;16(1):124. Epub 2021 Mar 10.

Division of Evolution and Genomic Sciences, Institute of Human Development, University of Manchester, Manchester, UK.

Background: The main genetic causes of homocystinuria are cystathionine beta-synthase (CBS) deficiency and the remethylation defects. Many patients present in childhood but milder forms may present later in life. Some countries have newborn screening programs for the homocystinurias but these do not detect all patients. Read More

Int J Mol Cell Med 2020 27;9(4):255-265. Epub 2021 Jan 27.

Animal Science Research Department, Yazd Agricultural and Natural Resources Research and Education Center, Agricultural Research, Education & Extension Organization (AREEO), Yazd, Iran.

Nuclear genetic mutations have been extensively investigated in solid tumors. However, the role of the mitochondrial genome remains uncertain. Since the metabolism of solid tumors is associated with aerobic glycolysis and high lactate production, tumors may have mitochondrial dysfunctions. Read More

Anal Chem 2021 03 3;93(10):4521-4527. Epub 2021 Mar 3.

Chemical Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India.

Clinicians require simple quantitative tools for the detection of homogentisic acid in alkaptonuria patients, a rare inherited disorder of amino acid metabolism. In this study, we report a whole-cell biosensor for homogentisic acid to detect alkaptonuria disease through the expression of green fluorescence protein. The assay system utilizes a promoter sequence (hmgA) isolated from the genome. Read More

Mol Cell Proteomics 2021 Feb 25;20:100065. Epub 2021 Feb 25.

Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden. Electronic address:

Drosophila melanogaster has been a workhorse of genetics and cell biology for more than a century. However, proteomic-based methods have been limited due to the complexity and dynamic range of the fly proteome and the lack of efficient labeling methods. Here, we advanced a chemically defined food source into direct stable-isotope labeling of amino acids in flies (SILAF). Read More

Brain Commun 2021 28;3(1):fcab002. Epub 2021 Jan 28.

Department of Medical Genetics, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.

A subset of individuals diagnosed with cerebral palsy will have an underlying genetic diagnosis. Previously, a missense variant in was described as a candidate mutation in a single family diagnosed with autosomal recessive spastic cerebral palsy-1 (CPSQ1; OMIM 603513). Following the ascertainment of a further branch of the CPSQ1 kindred, we found that the previously reported variant did not segregate with the neurological disease phenotype in the recently ascertained branch of the kindred. Read More

J Inherit Metab Dis 2021 Feb 17. Epub 2021 Feb 17.

Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.

Isolated methylmalonic acidaemia (MMA) and propionic acidaemia (PA) are rare inherited metabolic diseases. Six years ago, a detailed evaluation of the available evidence on diagnosis and management of these disorders has been published for the first time. The article received considerable attention, illustrating the importance of an expert panel to evaluate and compile recommendations to guide rare disease patient care. Read More

Medicine (Baltimore) 2021 Feb;100(5):e24007

Peking University Shenzhen Hospital.

Rationale: This study aimed to investigate the genetic mutation characteristics of congenital idiopathic hypogonadotropic hypogonadism (IHH) through the clinical features and genetic analysis of 2 patients with IHH in 1 pedigree.

Patient Concerns: A 23-year-old girl presented with primary amenorrhea, sparse pubic hair, lack of breast development, and delayed sexual development.

Diagnoses: Combined with the clinical characteristics, auxiliary examinations, and molecular genetic analysis, the patient was diagnosed as IHH. Read More

Curr Gene Ther 2021 Jan 26. Epub 2021 Jan 26.

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Background: Mucopolysaccharidosis type I (MPS I) is an inherited disorder caused by α-L-iduronidase (IDUA) deficiency. The available treatments are not effective in improving all signs and symptoms of the disease.

Objective: In the present study, we evaluated the transfection efficiency of repeated intravenous administrations of cationic nanoemulsions associated with the plasmid pIDUA (containing IDUA gene). Read More

Int J Environ Res Public Health 2021 Feb 9;18(4). Epub 2021 Feb 9.

Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.

Biotinidase (BTD) deficiency is an autosomal recessive inherited neurocutaneous disorder. BTD recycles the vitamin biotin, a coenzyme essential for the function of four biotin-dependent carboxylases, including propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase, pyruvate carboxylase, and acetyl-CoA carboxylase. Due to deficient activities of the carboxylases, BTD deficiency is also recognized as late-onset multiple carboxylase deficiency and is associated with secondary alterations in the metabolism of amino acids, carbohydrates, and fatty acids. Read More

Neurochem Int 2021 May 6;145:104984. Epub 2021 Feb 6.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, K7L 3N6, Canada; Department of Anesthesiology & Perioperative Medicine, Queen's University, Kingston, Ontario, K7L 3N6, Canada; Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, K7L 3N6, Canada. Electronic address:

Arginase-1 (Arg1) is an enzyme controlling the final step of the urea cycle, with highest expression in the liver and lower expression in the lungs, pancreas, kidney, and some blood cells. Arg1 deficiency is an inherited urea cycle disorder presenting with neurological dysfunction including spastic diplegia, intellectual and growth retardation, and encephalopathy. The contribution of Arg1 expression in the central and peripheral nervous system to the development of neurological phenotypes remains largely unknown. Read More

Int J Neonatal Screen 2020 Mar 14;6(1). Epub 2020 Mar 14.

Georgia Department of Public Health, Atlanta, GA 30303, USA.

Georgia uses post-analytical tools through Collaborative Laboratory Integrated Reports (CLIR) to triage abnormal newborn screening (NBS) results for follow-up. Condition specific tools are used to assign each case a risk level, which is used to guide follow-up recommendations. Follow-up recommendations include assessment by the child's primary care provider as well as testing, either a repeat NBS or confirmatory testing. Read More

World J Clin Cases 2021 Jan;9(3):697-706

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong Province, China.

Background: Juvenile-onset primary open-angle glaucoma (JOAG), characterized by severe elevation of intraocular pressure and optic neuropathy prior to the age of 40, is a rare subtype of primary open-angle glaucoma. Several genetic mutations have been associated with JOAG.

Case Summary: The proband patient was a young male, diagnosed with primary open-angle glaucoma at the age of 27. Read More

Zhonghua Er Ke Za Zhi 2021 Feb;59(2):125-130

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

To analyze the clinical and genetic features, as well as the treatment outcomes of two boys with nephrogenic syndrome of inappropriate antidiuresis (NSIAD) caused by gain-of-function mutations in the V2 vasopressin receptor gene (AVPR2). The clinical manifestations, genetic testing, therapeutic interventions and the outcomes of two boys with NSIAD hospitalized in the Department of Endocrinology, Beijing Children's Hospital in April 2019 were reported. A literature search with "Nephrogenic syndrome of inappropriate antidiuresis" and "AVPR2 gene" as keywords was conducted at the China national knowledge infrastructure (CNKI), the Wanfang Data Knowledge Service Platform, PubMed and Springer Link up to May 2020. Read More

Front Immunol 2020 14;11:606721. Epub 2021 Jan 14.

Laboratory of Genetics and Epigenetics of Human Diseases, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.

In recent years, immunotherapy has been revolutionized by a new approach that works by blocking receptors called immune checkpoints (IC). These molecules play a key role in maintaining immune homeostasis, mainly by suppressing the immune response and by preventing its overactivation. Since inhibition of the immune response by IC can be used by cancer to avoid recognition and destruction by immune system, blocking them enhances the anti-tumor response. Read More

PLoS One 2021 29;16(1):e0246114. Epub 2021 Jan 29.

Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA, United States of America.

Purpose: Mitochondrial (mt) DNA damage is associated with age-related macular degeneration (AMD) and other human aging diseases. This study was designed to quantify and characterize mtDNA low-frequency heteroplasmy single nucleotide polymorphisms (SNPs) of three different tissues isolated from AMD subjects using Next Generation Sequencing (NGS) technology.

Methods: DNA was extracted from neural retina, [RPE+choroid] and blood from three deceased age-related macular degeneration (AMD) subjects. Read More

Int J Mol Sci 2021 Jan 24;22(3). Epub 2021 Jan 24.

Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK.

Biallelic pathogenic variants in solute carrier family 38 member 8, , cause a pan-ocular autosomal recessive condition known as foveal hypoplasia 2, FVH2, characterised by foveal hypoplasia, nystagmus and optic nerve chiasmal misrouting. Patients are often clinically diagnosed with ocular albinism, but foveal hypoplasia can occur in several other ocular disorders. Here we describe nine patients from seven families who had molecularly confirmed biallelic recessive variants in identified through whole genome sequencing or targeted gene panel testing. Read More

Mol Genet Genomic Med 2021 Jan 19:e1559. Epub 2021 Jan 19.

Newborn Screening, Metabolic and Genetics Unit, Department of Human Genetics, National Institute of Health Dr Ricardo Jorge, Porto, Portugal.

Background: The impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Persistently high levels of phenylalanine lead to irreversible damage to the nervous system. Therefore, early diagnosis of the affected individuals is important, as it can prevent clinical manifestations of the disease. Read More