A novel mutation in YARS2 causes myopathy with lactic acidosis and sideroblastic anemia

2012 ◽  
Vol 33 (8) ◽  
pp. 1201-1206 ◽  
Author(s):  
Florin Sasarman ◽  
Tamiko Nishimura ◽  
Isabelle Thiffault ◽  
Eric A. Shoubridge
Keyword(s):  
Lactic Acidosis ◽  
Novel Mutation ◽  
Sideroblastic Anemia

scholarly journals A novel mutation in NDUFB11 unveils a new clinical phenotype associated with lactic acidosis and sideroblastic anemia

2016 ◽  
Vol 91 (3) ◽  
pp. 441-447 ◽  
Author(s):  
A. Torraco ◽  
M. Bianchi ◽  
D. Verrigni ◽  
V. Gelmetti ◽  
L. Riley ◽  
...  
Keyword(s):  
Lactic Acidosis ◽  
Clinical Phenotype ◽  
Novel Mutation ◽  
Sideroblastic Anemia

scholarly journals A Myopathy, Lactic Acidosis, Sideroblastic Anemia (Mlasa) Case Due to A Novel Pus1 Mutation

2017 ◽  
Author(s):  
Çiğdem Seher Kasapkara ◽  
Leyla Tümer ◽  
Nadia Zanetti ◽  
Fatih Ezgü ◽  
Eleonora Lamantea ◽  
...  
Keyword(s):  
Lactic Acidosis ◽  
Sideroblastic Anemia

A novel homozygous YARS2 mutation causes severe myopathy, lactic acidosis, and sideroblastic anemia 2

2014 ◽  
Vol 59 (4) ◽  
pp. 229-232 ◽  
Author(s):  
Junya Nakajima ◽  
Tuba F Eminoglu ◽  
Goksel Vatansever ◽  
Mitsuko Nakashima ◽  
Yoshinori Tsurusaki ◽  
...  
Keyword(s):  
Lactic Acidosis ◽  
Sideroblastic Anemia

scholarly journals Mutation of the Mitochondrial Tyrosyl-tRNA Synthetase Gene, YARS2, Causes Myopathy, Lactic Acidosis, and Sideroblastic Anemia—MLASA Syndrome

2010 ◽  
Vol 87 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Lisa G. Riley ◽  
Sandra Cooper ◽  
Peter Hickey ◽  
Joëlle Rudinger-Thirion ◽  
Matthew McKenzie ◽  
...  
Keyword(s):  
Lactic Acidosis ◽  
Trna Synthetase ◽  
Sideroblastic Anemia

scholarly journals A Novel Mutation in the Mitochondrial DNA CytochromebGene (MTCYB)in a Patient With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Strokelike Episodes Syndrome

2012 ◽  
Vol 28 (2) ◽  
pp. 236-242 ◽  
Author(s):  
Valentina Emmanuele ◽  
Evangelia Sotiriou ◽  
Purificación Gutierrez Rios ◽  
Jaya Ganesh ◽  
Rebecca Ichord ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Lactic Acidosis ◽  
Novel Mutation ◽  
Mitochondrial Encephalomyopathy

Three Kinships with ALAS2 P520L Mutations, Two in Association with Severe Iron Overload, and One with Sideroblastic Anemia and Severe Iron Overload.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3723-3723
Author(s):  
Pauline L. Lee ◽  
James C. Barton ◽  
Sreenivas V. Rao ◽  
Ronald T. Acton ◽  
Brian K. Adler ◽  
...  
Keyword(s):  
Iron Overload ◽  
Novel Mutation ◽  
White Male ◽  
Missense Mutations ◽  
Sideroblastic Anemia ◽  
Aminolevulinate Synthase ◽  
C282y Homozygote ◽  
Sequencing Studies ◽  
Unknown Gene ◽  
Distinctive Phenotype

Abstract Aminolevulinate synthase 2 (ALAS2) is an erythroid-expressed gene located on chromosome Xp11.21. Mutations in ALAS2 have been shown to be associated with sideroblastic anemia. We have identified a novel mutation in ALAS2, P520L, in three kinships. The P520L mutation was not found in 316 white male control subjects. The proline in this position is highly conserved across species from humans to zebrafish. In the C kinship, the P520L mutation was first identified in a white man who presented with severe iron overload at an early age and was a HFE C282Y homozygote. Genetic analyses of members of the C kinship suggest that the presence of P520L alone in hemizygous males, or simple heterozygosity in females, is not associated with anemia or iron overload. Females heterozygous for both HFE C282Y and ALAS2 P520L also had normal ferritin levels. Only subjects homozygous for HFE C282Y and hemizygous or heterozygous for ALAS2 P520L had severe iron overload. Sequencing studies revealed that the propositus did not have missense mutations in HAMP, HJV, FPN1, ABC7, IL6, or RAG1. In the H kinship, the propositus was a white woman with severe iron overload who was heterozygous for ALAS2 P520L; she had a wildtype HFE genotype. The pedigree of the H kinship identified 5 additional females who were heterozygous for the P520L ALAS2 mutation. Only the propositus had iron overload and none of the subjects with P520L had sideroblastic anemia. The propositus did not have missense mutations in FPN1, HAMP, HJV, TFR2, B2M, IRP2, ABC7, or SFT. We speculate that the propositus in the H kinship has a mutation in a currently unknown gene that contributes to her severe iron overload. In the S kinship, the P520L mutation was identified in a white man with sideroblastic anemia and severe iron overload. The patient had a second mutation in ALAS2, R560H, a mutation previously described in two brothers with sideroblastic anemia of variable penetrance (Blood100:4236–4238, 2002). It is not possible to determine the effect of the P520L mutation on the penetrance of the R560H-associated sideroblastic anemia and iron overload. We conclude that the ALAS2 P520L occurs at a very low allele frequency in the white population. The present observations also suggest that there is no distinctive phenotype associated with the P520L mutation alone, but that P520L may act as a modifier of iron overload in the presence of HFE homozygosity, other missense mutations of ALAS2, or mutations of uncharacterized iron regulatory genes.

A NOVEL Mutation of the Erythroid-Specific Aminolevulinate Synthase 2 Gene IN A Patient with Pyridoxine Responsive Sideroblastic Anemia and Deferasirox Responsive Hemochromatosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5105-5105
Author(s):  
Umran Caliskan ◽  
Huseyin Tokgoz ◽  
Hasan Yuksekkaya
Keyword(s):  
Novel Mutation ◽  
Hereditary Hemochromatosis ◽  
Gene Mutations ◽  
Chelating Agent ◽  
Peripheral Blood Smear ◽  
Microcytic Anemia ◽  
Hfe Gene ◽  
Sideroblastic Anemia ◽  
Aminolevulinate Synthase ◽  
Hypochromic Microcytic Anemia

Abstract Abstract 5105 A-14 years-old man, admitted to our clinic with weakness and paleness since one month. He has hepatosplenomegaly. Blood tests and peripheral blood smear showed anemia that severe hypochromic, microcytic anemia. There is ringed sideroblasts without dysplastic hematopoiesis in bone marrow cytology. Liver tests were normal. A liver biopsy showed heavy parenchymal iron deposition and grade-III fibrosis. Screening for HFE gene mutations was negative. MR imaging demonstrated that severe iron accumulation in liver and heart. ALAS2 gene screening showed that novel mutation in exon 7 (Gly390Gly, c.1170, C□T). Eventually, was diagnosed as sideroblastic anemia and hemochromatosis. He was treated successfully with pyridoxine and chelating agent (deferasirox, IGL-670). The findings suggest that the Gly390Gly in ALAS2 mutation causes sideroblastic anemia and hemochromatosis, without hereditary hemochromatosis gene mutations. This mutation cause sideroblastic anemia is clinically pyridoxine-responsive. Deferasirox is effective agent for reduce hepatic iron loading in this condition. Disclosures Off Label Use: deferasiroks was used for hemochromatosis secondary to congenital syderoblastic anemia.

scholarly journals The phenotypic spectrum of germline YARS2 variants: from isolated sideroblastic anemia to mitochondrial myopathy, lactic acidosis and sideroblastic anemia 2

Haematologica ◽  
2018 ◽  
Vol 103 (12) ◽  
pp. 2008-2015 ◽  
Author(s):  
Lisa G. Riley ◽  
Matthew M. Heeney ◽  
Joëlle Rudinger-Thirion ◽  
Magali Frugier ◽  
Dean R. Campagna ◽  
...  
Keyword(s):  
Lactic Acidosis ◽  
Mitochondrial Myopathy ◽  
Sideroblastic Anemia ◽  
Phenotypic Spectrum
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