Hb Knossos: HBB:c.82G&gt;T Associated with HBB:c.315+1G&gt;A Beta Zero Mutation Causes Thalassemia Intermedia

Nasouhipur, Hengameh; Banihashemi, Ali; Kamangar, Reza Youssefi; Akhavan‐Niaki, Haleh

doi:10.1007/s12288-014-0343-y

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…At 2012, we reported another case with co inheritance of Codon 8 and a mild β-globin mutation +22 5`UTR (G>A) that was missed in screening program (13). In Iran, Hb Knossos for the first time was reported from Mazandaran and in a case that like the presented case was compound heterozygote for c.82G>T and c.315+1G>A mutations (18). In that study, the Hb Knossos carrier had normal hematological indices.…”

Section: Discussionsupporting

confidence: 55%

Identification of a Neonate with Thalassemia Intermedia Despite Premarital Screening Program in Mazandaran Province (Co-inheritance of Hb Knossos and IVS II-1 G> A Mutations)

Karami

Jalali

Mahdavi³

et al. 2017

Res Mol Med (RMM)

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Background: Beta thalassemia is a common health problem in Iran especially in Northern provinces. Premarital screening for thalassemia is compulsory in Iran and identification of the carriers is based on primary CBC (Cell Blood Count) and hemoglobin electrophoresis. Silent mutations on β-globin gene have borderline or normal hematological indices that cannot be detected in premarital screening. Materials and methods: A four years old boy affected with β-thalassemia was referred to the lab for molecular analysis. During the screening program for β-thalassemia, his father and mother were diagnosed as α-and β-thalassemia carrier respectively. Results:The results of molecular analysis showed that in addition to the α-globin single gene deletion (α 3.7 ), the father had also carried a silent mutation on his β-globin gene named HBB c. 82G>T or Hb Knossos that was missed in screening program. Conclusion:The presented case shows that using CBC and hemoglobin electrophoresis in premarital screening program for detecting β-thalassemia carriers is not a valid approach and individuals who are carriers of silent β-globin gene mutations are missed in this procedure. Hence, in premarital screening program precise molecular investigation especially when the partner is a typical β-thalassemia carrier is recommended.

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Section: Discussionsupporting

confidence: 55%

Identification of a Neonate with Thalassemia Intermedia Despite Premarital Screening Program in Mazandaran Province (Co-inheritance of Hb Knossos and IVS II-1 G> A Mutations)

Karami

Jalali

Mahdavi³

et al. 2017

Res Mol Med (RMM)

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“…Hb Knossos mutation was reported to be linked to δ 0 -globin gene codon 59 [−A] mutation in the majority of North African and Mediterranean countries [25–27]. This combination correlated to normal or borderline red blood cell indices and also with low Hb A2 levels [25, 28]. In this study, the δ 0 codon 59 [−A] mutation was observed for the first time in a Syrian family, and it was associated with the β + Hb Knossos mutation for the proband and mother.…”

Section: Discussionmentioning

confidence: 99%

Hb Knossos (HBB: c.82G > T), β-globin CD 5 (−CT) (HBB: c.17_18delCT) and δ-globin CD 59 (−a) (HBD: c.179delA) mutations in a Syrian patient with β-thalassemia intermedia

2019

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Background Beta thalassemia (β-thal) is an inherited hemoglobin disorder characterized by reduced synthesis of the hemoglobin that results in microcytic hypochromic anemia. β-Thalassemia intermedia (TI) is a clinical term of intermediate gravity between the carrier state and β-thalassemia major (β -TM). Case presentation We describe a 12-year-old male proband originating from Al-Quneitra province - southwest Syria. Hematological investigations revealed, pallor and anemia (Hb 9 g/dl). The mean cell volume (MCV) 64 fL; mean cell hemoglobin (MCH) 21.8 pg. Capillary electrophoresis (CE) electropherogram revealed low level of Hb A1 (36.2%), high level of Hb F (62.2%) and low level of Hb A2 (1.6%). The proband requires blood transfusion occasionally. Direct DNA sequencing and Polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) for mutations detection were used. The molecular analysis revealed the presence of rare β + Hb Knossos codon 27 (G > T) (HBB: c.82G > T) variant associated with β 0 codon 5 [−CT] (HBB: c.17_18delCT) mutation in beta-globin (β-globin) gene and δ 0 codon 59 [−A] (HBD: c.179delA) mutation in delta-globin (δ-globin) gene. The proband tested negative for the common deletional forms of alpha thalassemia (α-thal). Polymorphism of the Xmn-I locus (HBG2: c.-211C > T) revealed that the proband had a homozygous [TT] for Xmn-1 locus. Conclusions To our knowledge, this is the first report of beta thalassemia intermedia due to combination of Hb Knossos /codon 5 [−CT] associated with δ 0 codon 59 [−A] in Syrian patient. On the other hand, in Syria, β-thal carriers who have low level of Hb A2 due to decreased δ-chain production, different δ-thal gene mutations must be screened to avoid the failure diagnosis of β-thal disease.

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“…При представения клиничен случай 1 лабораторни данни за таласемия минор има само при единия родител, докато клиниката на пациента (включително нуждата от хемотрансфузии) не кореспондира с носителски статус. Разкритото с генетичен анализ носителство на HbKnossos при другия родител не се асоциира с клинична симптоматика и не води до промяна в лабораторните показатели от електрофорезата на хемоглобин, което е в съответствие с докладваното в различни бази данни [11][12][13]. Провеждането на генетични изследвания при пробанда и родителите е препоръчително във всички случаи на бета-таласемия и особено полезно при пациенти с нетипична клиника.…”

Section: обсъжданеunclassified

Генетична Диагностика На Бета-Таласемия В България – Какво Научихме От Нашите Пациенти

Андонова,

Брадинова,

Савов

2023

Редки болести и лекарства сираци

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Бета-таласемията e наследствено автозомно-рецесивно състояние. Дължи се на нарушена структура и функция на хемоглобина и има висока честота в района на Средиземноморието, включително и България. Заболяването е добре познато на специалистите, но диагнозата може да бъде предизвикателство при някои пациенти поради широкия спектър на клинична изява и големия брой подлежащи генетични варианти с уникално съчетание между тях. В настоящото проучване са включени 572 семейства от нашата страна, като майорна β-таласемия е доказана при 195 от индексните пациенти (57 хомозиготи и 138 двойни/съставни хетерозиготи), а минорна β-таласемия – при 609 изследвани индивиди. Дородова диагностика е извършена при 107 семейства със 131 изследвани фетуса – от тях 27 са засегнати, 65 са носители и 39 са неносители. Предимплантационна генетична диагностика има при 8 семейства с изследвани 48 ембриона – 11 са определени като засегнати, 24 – са носители и 14 – неносители. Идентифицирани са общо 35 различни патологични генетични варианта в НВВ гена. Най-честите сред тях са IVS1-110, bo39, IVS1-6, IVS2-745, IVS1-1 и Fsh5; открити са и мутации, асоциирани с HbS, Hb Knossos, HbG-Coushatta, HbO-Arabia. Представяме и 4 клинични случаи с нетипична клиника или с пропуски в оценката на носителския статус при членове на семействата. Показана е важната роля на генетичното охарактеризиране на мутационния статус в семейството за поставяне на точна диагноза, ефективна профилактика чрез пренатална и предимплантационна диагностика и провеждане на медико-генетична консултация. Необходими са сравнително малко усилия и предоставянето на системна информация към гражданското общество и здравните специалисти за постигане на оптимален ефект в лечението и профилактиката на това заболяване, особено когато се касае за планиране или проследяване на бременност.

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Hb Knossos: HBB:c.82G>T Associated with HBB:c.315+1G>A Beta Zero Mutation Causes Thalassemia Intermedia

Cited by 5 publications

References 14 publications

Identification of a Neonate with Thalassemia Intermedia Despite Premarital Screening Program in Mazandaran Province (Co-inheritance of Hb Knossos and IVS II-1 G> A Mutations)

Identification of a Neonate with Thalassemia Intermedia Despite Premarital Screening Program in Mazandaran Province (Co-inheritance of Hb Knossos and IVS II-1 G> A Mutations)

Hb Knossos (HBB: c.82G > T), β-globin CD 5 (−CT) (HBB: c.17_18delCT) and δ-globin CD 59 (−a) (HBD: c.179delA) mutations in a Syrian patient with β-thalassemia intermedia

Генетична Диагностика На Бета-Таласемия В България – Какво Научихме От Нашите Пациенти

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