Nucleotide-binding leucine-rich repeat (NLR) disease resistance genes typically confer resistance against races of a single pathogen. Here, we report that Yr87/Lr85, an NLR gene from Aegilops sharonensis and Aegilops longissima, confers resistance against both P. striiformis tritici (Pst) and Puccinia triticina (Pt) that cause stripe and leaf rust, respectively.
View Article and Find Full Text PDFDuring the past two decades, an emerging group of genes coding for proteins involved in glycosylphosphatidylinositol (GPI) anchor biosynthesis are being implicated in early-infantile epileptic encephalopathy. Amongst these, a hypomorphic promoter mutation in the mannosyltransferase-encoding PIGM gene was described in seven patients to date, exhibiting intractable absence epilepsy, portal and cerebral vein thrombosis and intellectual disability (ID). We describe here three siblings exhibiting intractable epilepsy and ID, found to harbor a homozygous c.
View Article and Find Full Text PDFLong-term genetic studies of wild populations are very scarce, but are essential for connecting ecological and population genetics models, and for understanding the dynamics of biodiversity. We present a study of a wild wheat population sampled over a 36-year period at high spatial resolution. We genotyped 832 individuals from regular sampling along transects during the course of the experiment.
View Article and Find Full Text PDFJ Inherit Metab Dis
September 2024
Dihydrolipoamide dehydrogenase (DLD) deficiency is an ultra-rare autosomal-recessive inborn error of metabolism, affecting no less than five mitochondrial multienzyme complexes. With approximately 30 patients reported to date, DLD deficiency was associated with three major clinical presentations: an early-onset encephalopathic phenotype with metabolic acidosis, a predominantly hepatic presentation with liver failure, and a rare myopathic phenotype. To elucidate the demographic, phenotypic, and molecular characteristics of patients with DLD deficiency within the Israeli population, data were collected from metabolic disease specialists in four large tertiary medical centers in the center and south of Israel.
View Article and Find Full Text PDFTopoisomerase 3α (TOP3A) is an enzyme that removes torsional strain and interlinks between DNA molecules. TOP3A localises to both the nucleus and mitochondria, with the two isoforms playing specialised roles in DNA recombination and replication respectively. Pathogenic variants in TOP3A can cause a disorder similar to Bloom syndrome, which results from bi-allelic pathogenic variants in BLM, encoding a nuclear-binding partner of TOP3A.
View Article and Find Full Text PDFStressed plants show altered phenotypes, including changes in color, smell, and shape. Yet, airborne sounds emitted by stressed plants have not been investigated before. Here we show that stressed plants emit airborne sounds that can be recorded from a distance and classified.
View Article and Find Full Text PDFHereditary orotic aciduria is an extremely rare, autosomal recessive disease caused by deficiency of uridine monophosphate synthase. Untreated, affected individuals may develop refractory megaloblastic anemia, neurodevelopmental disabilities, and crystalluria. Newborn screening has the potential to identify and enable treatment of affected individuals before they become significantly ill.
View Article and Find Full Text PDFGenetic conditions contribute a significant portion of disease etiologies in children admitted to general pediatric wards worldwide. While exome sequencing (ES) has improved clinical diagnosis and management over a variety of pediatric subspecialties, it is not yet routinely used by general pediatric hospitalists. We aim to investigate the impact of exome sequencing in sequencing-naive children suspected of having monogenic disorders while receiving inpatient care.
View Article and Find Full Text PDFGalactosemia is an inborn disorder of carbohydrate metabolism of which early detection can prevent severe illness. Although the assay for galactose-1-phosphate uridyltransferase (GALT) enzyme activity has been available since the 1960s, many issues prevented it from becoming universal. In order to develop the Israeli newborn screening pilot algorithm for galactosemia, flow injection analysis tandem mass spectrometry measurement of galactose-1-phosphate in archived dried blood spots from newborns with classical galactosemia, galactosemia variants, epimerase deficiency, and normal controls, was conducted.
View Article and Find Full Text PDFCongenital diarrheas and enteropathies (CODEs) constitute a heterogeneous group of individually rare disorders manifesting with infantile-onset chronic diarrhea. Genomic deletions in chromosome 16, encompassing a sequence termed the 'intestine-critical region (ICR)', were recently identified as the cause of an autosomal recessive congenital enteropathy. The regulatory sequence within the ICR is flanked by an unannotated open reading frame termed PERCC1, which plays a role in enteroendocrine cell (EEC) function.
View Article and Find Full Text PDFPurpose: The clinical spectrum of motile ciliopathies includes laterality defects, hydrocephalus, and infertility as well as primary ciliary dyskinesia when impaired mucociliary clearance results in otosinopulmonary disease. Importantly, approximately 30% of patients with primary ciliary dyskinesia lack a genetic diagnosis.
Methods: Clinical, genomic, biochemical, and functional studies were performed alongside in vivo modeling of DAW1 variants.
Hermansky-Pudlak syndrome (HPS) is a group of rare autosomal recessive disorders characterized by oculocutaneous albinism (OCA) and bleeding diathesis. To date, 11 HPS types have been reported (HPS-1 to HPS-11), each defined by disease-causing variants in specific genes. Variants in the gene were found in approximately 15% of HPS patients, most of whom harbor the Puerto Rican founder mutation.
View Article and Find Full Text PDFAvoidance of fasting and regular ingestion of uncooked-cornstarch have long been the mainstay dietary treatment of Glycogen Storage Disease type Ia (GSD-Ia). However, GSD-Ia patients who despite optimal dietary treatment show poor glycemic control and are intolerant to cornstarch, present a complex clinical challenge. We pursued Whole Exome Sequencing (WES) in three such unrelated patients, to both confirm a molecular diagnosis of GSD-Ia, and seek additional variants in other genes (e.
View Article and Find Full Text PDFA total of 353 urediniospore isolates of f. sp. () collected in Israel during 2001 to 2019 were analyzed.
View Article and Find Full Text PDFBackground: HPS-1 is a genetic type of Hermansky-Pudlak syndrome (HPS) with highly penetrant pulmonary fibrosis (HPSPF), a restrictive lung disease that is similar to idiopathic pulmonary fibrosis (IPF). Hps1 (pale ear) is a naturally occurring HPS-1 mouse model that exhibits high sensitivity to bleomycin-induced pulmonary fibrosis (PF). Traditional methods of administering bleomycin as an intratracheal (IT) route to induce PF in this model often lead to severe acute lung injury and high mortality rates, complicating studies focusing on pathobiological mechanisms or exploration of therapeutic options for HPSPF.
View Article and Find Full Text PDFPhosphopantothenoylcysteine synthetase (PPCS) catalyzes the second step of the de novo coenzyme A (CoA) synthesis starting from pantothenate. Mutations in PPCS cause autosomal-recessive dilated cardiomyopathy, often fatal, without apparent neurodegeneration, whereas pathogenic variants in PANK2 and COASY, two other genes involved in the CoA synthesis, cause Neurodegeneration with Brain Iron Accumulation (NBIA). PPCS-deficiency is a relatively new disease with unclear pathogenesis and no targeted therapy.
View Article and Find Full Text PDFSanfilippo Syndrome, or mucopolysaccharidosis type III (MPS III), is a group of autosomal-recessive lysosomal storage disorders leading to tissue accumulation of heparan sulfate. MPS III is caused by deficiency in one of 4 enzymes involved in lysosomal degradation of heparan sulfate. Based on the relevant enzyme deficiency, 4 types have been recognized.
View Article and Find Full Text PDFBackground: The endocytic reabsorption of proteins in the proximal tubule requires a complex machinery and defects can lead to tubular proteinuria. The precise mechanisms of endocytosis and processing of receptors and cargo are incompletely understood. EHD1 belongs to a family of proteins presumably involved in the scission of intracellular vesicles and in ciliogenesis.
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