Prolonged Thrombocytopenia in a Child with Severe Neonatal Alloimmune Reaction and Noonan Syndrome

Fetomaternal alloimmune thrombocytopenia (FMAIT) caused by maternal antibodies is the leading cause of severe neonatal thrombocytopenia. A 1-month-old Caucasian girl was referred to our Hematology Clinic for persistent thrombocytopenia diagnosed after a bleeding episode. Diagnostic tests suggested FMAIT. Mild thrombocytopenia persisted for 18 months, and subsequent findings of dysmorphic facies, short stature and mild pulmonary stenosis led to the hypothesis of Noonan syndrome (NS), which was confirmed by genetic test. Other hematological abnormalities were excluded and she had no further bleeding episodes. This case illustrates the possibility of different diagnoses with the same clinical manifestations. The persistence of thrombocytopenia longer than expected associated with typical physical features led to the diagnosis of NS.info:eu-repo/semantics/publishedVersio

Wide spectrum of F9 variants in hemophilia B families from the Portuguese population

Introduction: Hemophilia B is an X-linked bleeding disorder caused by molecular defects in the Factor IX gene (F9), leading to either deficiency or functional abnormality of Factor IX. Actual data indicate a high heterogeneity of variants in F9. Over 1000 different variants have been reported, including pathogenic single nucleotide variants (SNPs), indels and complex variants. Materials and Methods: 86 index patients and 313 relatives were studied. F9 variant analysis was performed from total genomic DNA by PCR followed either by SSCP and DNA sequencing or direct DNA sequencing. When no variant was detected by sequencing, F9 analysis by MLPA was performed. Segregation studies were performed in each family. Results: Overall, 52 different F9 variants have been identified, including 49 SNPs or small indels, a gross duplication (exons 2-6) and two deletions of the entire gene. Ten of the variants had been firstly reported by us and three are novel: c.391+5G>T; c.432T>G, p.(Phe144Leu) and c.749C>A, p.(Ala250Glu). This approach allowed establishing the carrier state of over 300 women and 12 prenatal diagnoses were performed. Conclusions: The spectrum of F9 variants identified in the Portuguese population significantly overlaps that observed in other populations. Identification of F9 gene variants in patients allows genotype-phenotype correlations and carrier detection, as well as prenatal diagnosis. Sanger sequencing of the coding region and adjacent intronic sequences of F9 still remains a valid and effective tool for the molecular study of hemophila B, providing information for appropriate genetic counseling and new insights regarding the molecular basis of the pathology.info:eu-repo/semantics/publishedVersio

Sickle cell anemia - nitric oxide related genetic modifiers of hematological and biochemical parameters

BACKGROUND: Sickle cell anemia (SCA) is an inherited blood disorder. SCA patients present clinical and hematologic variability that cannot be only explained by the single mutation in the beta-globin gene. Others genetic modifiers and environmental effects are important for the clinical phenotype. SCA patients present arginine deficiency that contributes to a lower nitric oxide (NO) bioactivity. OBJECTIVE: The aim of this work is to determine the association between hematological and biochemical parameters and genetic variants from eNOS gene, in pediatric SCA patients. METHODS: 26 pediatric SCA patients were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques in three important eNOS gene polymorphisms - rs2070744, rs1799983 and intron 4 VNTR. RESULTS: Results from this study show a significant statistical association between some parameters and genetic variants: an increased reticulocyte count and high serum lactate dehydrogenase levels were associated with both the rs2070744 TTand the rs1799983 GG genotypes at eNOS gene and high levels of neutrophils were associated with the eNOS4a allele. CONCLUSIONS: Our results reinforce the importance of NO bioactivity in SCA. We presume that NO, and its precursors might be used as therapy to improve the quality of life of SCA patients.info:eu-repo/semantics/publishedVersio

Publisher Correction: Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromes (Nature Medicine, (2021), 27, 10, (1806-1817), 10.1038/s41591-021-01511-6)

In the version of this Article initially published, there were errors in Fig. 1. Specifically, in the top right box in Fig. 1a, the text now reading “n = 25” mistakenly read “125” in the original publication. Further, in the four graphs of Fig. 1e, the colored labels “Wild-type,” “SAMD9/9Lmut” and “GATA2mut” were misaligned to the n and P values at their right. These errors have been corrected in the online version of the article