Clinical and genetic features of congenital dyserythropoietic anemia (CDA)

Autor:	Manuel Méndez, María-Isabel Moreno-Carralero, Adela-María Periago-Peralta, Angelina Lemes-Castellano, María-Pilar Ricard-Andrés, Saul Horta-Herrera, Marta Morado-Arias, Silvia de-la-Iglesia-Iñigo, Laura Llorente-González, María-Teresa Cedena-Romero, María-José Morán-Jiménez, Mariola Abio-Calvete, Fernando-Ataúlfo González-Fernández
Rok vydání:	2018
Předmět:	Ineffective erythropoiesis Adult Male Adolescent Genotype In silico Biology medicine.disease_cause 03 medical and health sciences symbols.namesake Young Adult 0302 clinical medicine medicine Humans Genetic Predisposition to Disease Child Gene Alleles Genetic Association Studies Aged Anemia Dyserythropoietic Congenital Glycoproteins Genetics Sanger sequencing Aged 80 and over Comparative Genomic Hybridization Massive parallel sequencing Genetic Variation High-Throughput Nucleotide Sequencing Nuclear Proteins GATA1 Hematology General Medicine Middle Aged medicine.disease Phenotype 030220 oncology & carcinogenesis Child Preschool symbols Female Congenital dyserythropoietic anemia Databases Nucleic Acid 030215 immunology
Zdroj:	European journal of haematology. 101(3)
ISSN:	1600-0609
Popis:	Introduction Congenital dyserythropoietic anemias (CDA) are characterized by hyporegenerative anemia with inadequate reticulocyte values, ineffective erythropoiesis, and hemolysis. Distinctive morphology of bone marrow erythroblasts and identification of causative genes allow classification into 4 types caused by variants in CDAN1, c15orf41, SEC23B, KIF23, and KLF1 genes. Objective Identify pathogenic variants in CDA patients. Methods Massive parallel sequencing with a targeted gene panel, Sanger sequencing, Comparative Genome Hybridization (CGH), and in silico predictive analysis of pathogenicity. Results Pathogenic variants were found in 21 of 53 patients studied from 44 unrelated families. Six variants were found in CDAN1: two reported, p.Arg714Trp and p.Arg725Trp and, four novel, p.Arg623Trp, p.Arg946Trp, p.Phe1125Ser and p.Ser1227Gly. Twelve variants were found in SEC23B: seven reported, p.Arg14Trp, p.Glu109Lys, p.Arg217Ter, c.835-2A>G, p.Arg535Ter, p.Arg550Ter and p.Arg718Ter and, five novel, p.Val164Leu, p.Arg190Gln, p.Gln521Ter, p.Arg546Trp, and p.Arg611Gln. The variant p.Glu325Lys in KLF1 was found in one patient and p.Tyr365Cys in ALAS2 in an other. Moreover, we identified genomic rearrangements by CGH in some SEC23B-monoallelic patients. Conclusions New technologies for genetic studies will help to find variants in other genes, in addition to those known, that contribute to or modulate the CDA phenotype or support the correct diagnosis.
Databáze:	OpenAIRE
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