scholarly journals Diseases Associated with Defects in tRNA CCA Addition

2020 ◽  
Vol 21 (11) ◽  
pp. 3780 ◽  
Author(s):  
Angelo Slade ◽  
Ribal Kattini ◽  
Chloe Campbell ◽  
Martin Holcik
Keyword(s):  
Retinitis Pigmentosa ◽  
B Cell ◽  
Developmental Delay ◽  
Cellular Systems ◽  
Loss Of Function ◽  
Partial Loss ◽  
Sideroblastic Anemia ◽  
Current State ◽  
Nucleotidyl Transferase ◽  
Essential Enzyme

tRNA nucleotidyl transferase 1 (TRNT1) is an essential enzyme catalyzing the addition of terminal cytosine-cytosine-adenosine (CCA) trinucleotides to all mature tRNAs, which is necessary for aminoacylation. It was recently discovered that partial loss-of-function mutations in TRNT1 are associated with various, seemingly unrelated human diseases including sideroblastic anemia with B-cell immunodeficiency, periodic fevers and developmental delay (SIFD), retinitis pigmentosa with erythrocyte microcytosis, and progressive B-cell immunodeficiency. In addition, even within the same disease, the severity and range of the symptoms vary greatly, suggesting a broad, pleiotropic impact of imparting TRNT1 function on diverse cellular systems. Here, we describe the current state of knowledge of the TRNT1 function and the phenotypes associated with mutations in TRNT1.

scholarly journals Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD)

Blood ◽  
2014 ◽  
Vol 124 (18) ◽  
pp. 2867-2871 ◽  
Author(s):  
Pranesh K. Chakraborty ◽  
Klaus Schmitz-Abe ◽  
Erin K. Kennedy ◽  
Hapsatou Mamady ◽  
Turaya Naas ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Loss Of Function ◽  
Partial Loss ◽  
Sideroblastic Anemia ◽  
Key Points ◽  
Congenital Sideroblastic Anemia

Key PointsSIFD is a syndromic form of congenital sideroblastic anemia associated with immunodeficiency, periodic fevers, and developmental delay. SIFD is due to partial loss-of-function mutations in the CCA-adding enzyme TRNT1.

Biallelic TRNT1 variants in a child with B cell immunodeficiency, periodic fever and developmental delay without sideroblastic anemia (SIFD variant)

2020 ◽  
Vol 225 ◽  
pp. 64-65
Author(s):  
Donato Rigante ◽  
Emilia Stellacci ◽  
Chiara Leoni ◽  
Roberta Onesimo ◽  
Francesca Clementina Radio ◽  
...  
Keyword(s):  
B Cell ◽  
Developmental Delay ◽  
Periodic Fever ◽  
Sideroblastic Anemia

scholarly journals A novel syndrome of congenital sideroblastic anemia, B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD)

Blood ◽  
2013 ◽  
Vol 122 (1) ◽  
pp. 112-123 ◽  
Author(s):  
Daniel H. Wiseman ◽  
Alison May ◽  
Stephen Jolles ◽  
Philip Connor ◽  
Colin Powell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Developmental Delay ◽  
Bone Marrow Transplant ◽  
Marrow Transplant ◽  
Clinical Syndrome ◽  
Sideroblastic Anemia ◽  
Key Points ◽  
Congenital Sideroblastic Anemia

Key Points A novel clinical syndrome of CSA, B-cell immunodeficiency, periodic fevers, and developmental delay is described. Bone marrow transplant resulted in complete and durable resolution of the hematologic and immunologic manifestations.

scholarly journals Abcb7, the gene responsible for X-linked sideroblastic anemia with ataxia, is essential for hematopoiesis

Blood ◽  
2006 ◽  
Vol 109 (8) ◽  
pp. 3567-3569 ◽  
Author(s):  
Corinne Pondarre ◽  
Dean R. Campagna ◽  
Brendan Antiochos ◽  
Lindsay Sikorski ◽  
Howard Mulhern ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Heme Biosynthesis ◽  
Atp Binding ◽  
Loss Of Function ◽  
Partial Loss ◽  
Sideroblastic Anemia ◽  
Atp Binding Cassette Transporter ◽  
Atp Binding Cassette

AbstractX-linked sideroblastic anemia with ataxia (XLSA/A) is a rare syndromic form of inherited sideroblastic anemia associated with spinocerebellar ataxia, and is due to mutations in the mitochondrial ATP-binding cassette transporter Abcb7. Here, we show that Abcb7 is essential for hematopoiesis and formally demonstrate that XLSA/A is due to partial loss of function mutations in Abcb7 that directly or indirectly inhibit heme biosynthesis.

scholarly journals Congenital sideroblastic anemia associated with B cell immunodeficiency, periodic fevers, and developmental delay: A case report and review of mucocutaneous features

2019 ◽  
Vol 7 ◽  
pp. 2050313X1987671
Author(s):  
Abdulhadi Jfri ◽  
Therese El-Helou ◽  
Kevin A. Watters ◽  
Annie Bélisle ◽  
Ivan V. Litvinov ◽  
...  
Keyword(s):  
Case Report ◽  
B Cell ◽  
Developmental Delay ◽  
Lichen Sclerosus ◽  
Sideroblastic Anemia ◽  
Febrile Episodes ◽  
Congenital Sideroblastic Anemia

This is a 40-year-old woman with sideroblastic anemia with B cell immunodeficiency, periodic fevers, and developmental delay syndrome, who has genital and extragenital lichen sclerosus on the abdomen and the upper back that have become erythematous and painful during febrile episodes. This report summarizes the published cases of sideroblastic anemia with B cell immunodeficiency, periodic fevers, and developmental delay and highlights associated mucocutaneous features.

scholarly journals Roles for RNA export factor, Nxt1, in ensuring muscle integrity and normal RNA expression in Drosophila

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin van der Graaf ◽  
Katia Jindrich ◽  
Robert Mitchell ◽  
Helen White-Cooper
Keyword(s):  
Mrna Export ◽  
Rna Stability ◽  
Muscle Degeneration ◽  
Loss Of Function ◽  
Cellular Functions ◽  
Partial Loss ◽  
Export Pathway ◽  
Pathway Gene ◽  
Rna Export

Abstract The mRNA export pathway is responsible for the transport of mRNAs from the nucleus to the cytoplasm, and thus is essential for protein production and normal cellular functions. A partial loss of function allele of the mRNA export factor Nxt1 in Drosophila shows reduced viability and sterility. A previous study has shown that the male fertility defect is due to a defect in transcription and RNA stability, indicating the potential for this pathway to be implicated in processes beyond the known mRNA transport function. Here we investigate the reduced viability of Nxt1 partial loss of function mutants, and describe a defect in growth and maintenance of the larval muscles, leading to muscle degeneration. RNA-seq revealed reduced expression of a set of mRNAs, particularly from genes with long introns in Nxt1 mutant carcass. We detected differential expression of circRNA, and significantly fewer distinct circRNAs expressed in the mutants. Despite the widespread defects in gene expression, muscle degeneration was rescued by increased expression of the costamere component tn (abba) in muscles. This is the first report of a role for the RNA export pathway gene Nxt1 in the maintenance of muscle integrity. Our data also links the mRNA export pathway to a specific role in the expression of mRNA and circRNA from common precursor genes, in vivo.

scholarly journals The de novo CACNA1A pathogenic variant Y1384C associated with hemiplegic migraine, early onset cerebellar atrophy and developmental delay leads to a loss of Cav2.1 channel function

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Maria A. Gandini ◽  
Ivana A. Souza ◽  
Laurent Ferron ◽  
A. Micheil Innes ◽  
Gerald W. Zamponi
Keyword(s):  
Developmental Delay ◽  
Early Onset ◽  
Structural Damage ◽  
De Novo ◽  
Splice Variants ◽  
Cerebellar Atrophy ◽  
Familial Hemiplegic Migraine ◽  
Significant Loss ◽  
Loss Of Function ◽  
Hemiplegic Migraine

AbstractCACNA1A pathogenic variants have been linked to several neurological disorders including familial hemiplegic migraine and cerebellar conditions. More recently, de novo variants have been associated with severe early onset developmental encephalopathies. CACNA1A is highly expressed in the central nervous system and encodes the pore-forming CaVα1 subunit of P/Q-type (Cav2.1) calcium channels. We have previously identified a patient with a de novo missense mutation in CACNA1A (p.Y1384C), characterized by hemiplegic migraine, cerebellar atrophy and developmental delay. The mutation is located at the transmembrane S5 segment of the third domain. Functional analysis in two predominant splice variants of the neuronal Cav2.1 channel showed a significant loss of function in current density and changes in gating properties. Moreover, Y1384 variants exhibit differential splice variant-specific effects on recovery from inactivation. Finally, structural analysis revealed structural damage caused by the tyrosine substitution and changes in electrostatic potentials.

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