IthaPhen: An Interactive Database of Genotype-Phenotype Data for Hemoglobinopathies

Xenophontos, Maria; Minaidou, Anna; Stephanou, Coralea; Tamana, Stella; Kleanthous, Marina; Kountouris, Petros

doi:10.1097/hs9.0000000000000922

Cited by 4 publications

(4 citation statements)

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“…It is also valuable for the study of rare diseases, such as hemoglobinopathies and other rare anemias that often have limited sample sizes and fragmented data. The genotype-phenotype data featured in this paper is openly available on the IthaPhen database [11]. Despite detailing the minimum standards in screening and diagnosis in this study, it is essential to acknowledge the importance of a more thorough understanding.…”

Section: Discussionmentioning

confidence: 99%

“…Hb, hemoglobin; HbA 2 , A 2 hemoglobin; HbF, F hemoglobin; MCH, mean corpuscular hemoglobin; MCV, mean corpuscular volume; MCHC, mean corpuscular hemoglobin concentration; NTDT, Non-transfusion-dependent thalassemia; PCV, packed cell volume; RBC, red blood cell count; RDW, red cell distribution; SD, standard deviation; TDT, transfusion-dependent thalassemia. Normal range (as reported in IthaPhen [11]): Hb 11.5-16.5 (female), 13-18 (male); RBC 3.8-5.8 (female), 4.5-6.5 (male); PCV 37-47 (female), 40-52 (male); MCV 80-100; MCH 27-32, MCHC 32-36; HbA 2 1.8-3; RDW, <15; HbF, <1.5.…”

Section: Case-level and Segregation Datamentioning

confidence: 91%

“…This study is a report of the clinical experience of the assay concealing any description or personal information of the individual case. All data were de-identified to protect the privacy of participants and submitted to IthaPhen (https://www.ithanet.eu/db/ithaphen) [11], accessed on 18 September 2023.…”

Section: Ethics Statement and Study Participantsmentioning

confidence: 99%

“…However, when combined with severe β + or β 0 alleles, it manifests a thalassemia intermedia phenotype [9,10]. Variant-to-phenotype associations have been described so far for four heterozygotes and six compound heterozygotes (available in IthaPhen [11]). Caselevel and segregation data are important in the evaluation of variant pathogenicity using the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) best-practice guidelines [12,13] while insufficient numbers of independent cases can contribute to the classification of variants as variants of uncertain significance (VUS).…”

Section: Introductionmentioning

confidence: 99%

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Unravelling the Complexity of the +33 C>G [HBB:c.-18C>G] Variant in Beta Thalassemia

Stephanou,

Petrou,

Kountouris

et al. 2024

Biomedicines

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The +33 C>G variant [NM_000518.5(HBB):c.-18C>G] in the 5′ untranslated region (UTR) of the β-globin gene is described in the literature as both mild and silent, while it causes a phenotype of thalassemia intermedia in the presence of a severe β-thalassemia allele. Despite its potential clinical significance, the determination of its pathogenicity according to established standards requires a greater number of published cases and co-segregation evidence than what is currently available. The present study provides an extensive phenotypic characterization of +33 C>G using 26 heterozygous and 11 compound heterozygous novel cases detected in Cyprus and employs computational predictors (CADD, RegulomeDB) to better understand its impact on clinical severity. Genotype identification of globin gene variants, including α- and δ-thalassemia determinants, and rs7482144 (XmnI) was carried out using Sanger sequencing, gap-PCR, and restriction enzyme digestion methods. The heterozygous state of +33 C>G had a silent phenotype without apparent microcytosis or hypochromia, while compound heterozygosity with a β+ or β0 allele had a spectrum of clinical phenotypes. Awareness of the +33 C>G is required across Mediterranean populations where β-thalassemia is frequent, particularly in Cyprus, with significant relevance in population screening and fetal diagnostic applications.

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Section: Discussionmentioning

confidence: 99%

Section: Case-level and Segregation Datamentioning

confidence: 91%

Section: Ethics Statement and Study Participantsmentioning

confidence: 99%