A Novel Deletion/Insertion Caused by a Replication Error in the β-Globin Gene Locus Control Region

Abstract

Deletions in the β-globin locus control region (β-LCR) lead to (εγδβ)(0)-thalassemia [(εγδβ)(0)-thal]. In patients suffering from these rare deletions, a normal hemoglobin (Hb), phenotype is found, contrasting with a hematological thalassemic phenotype. Multiplex-ligation probe amplification (MLPA) is an efficient tool to detect β-LCR deletions combined with long-range polymerase chain reaction (PCR) and DNA sequencing to pinpoint deletion breakpoints. We present here a novel 11,155 bp β-LCR deletion found in a French Caucasian patient which removes DNase I hypersensitive site 2 (HS2) to HS4 of the β-LCR. Interestingly, a 197 bp insertion of two inverted sequences issued from the HS2-HS3 inter-region is present and suggests a complex rearrangement during replication. Carriers of this type of thalassemia can be misdiagnosed as an α-thal trait. Consequently, a complete α- and β-globin gene cluster analysis is required to prevent a potentially damaging misdiagnosis in genetic counselling.

Alcoholic-Hepatitis, Links to Brain and Microbiome: Mechanisms, Clinical and Experimental Research

“…Interactions between alcohol and prescription drugs are common, particularly the additive effects with benzodiazepines and also with some of the antihistamine drugs; other interactions may occur with tricyclic antidepressants [137]. An important additional element of the hepatotoxic threat of alcohol is its enhancement of the hepatotoxic effects of other hepatotoxins (e.g., CCl 4 ) and even some drugs (e.g., acetaminophen) [138][139][140][141][142][143][144][145][146][147][148].…”

Identification and molecular characterization of a novel 163 kb deletion: The Italian (ϵγδβ)0-thalassemia

“…To test the significance of these values, we looked for the phenotype of the (εγδβ) 0 -thalassemia carriers from literature (Table 2). [3][4][5][6][16][17][18][19][28][29][30] We compared (i) the Hb A2 values of the 19 (εγδβ) 0 -thalassemia Figure 3 Comparison of the HbA2 and Hb values between (εγδβ) 0 -thalassemia and α 0 -and β 0 -thalassemia carriers. (A) Histogram of the Hb A2 value of 92 heterozygotes for α 0 -thalassemia and of the 19 heterozygotes for (εγδβ) 0 -thalassemia from literature.…”

Beta-thalassemias: molecular, epidemiological, diagnostical and clinical aspects

“…Ce blocage est dû à la délétion de la région située entre les gènes A ␥ et ␦, zone de fixation de la protéine BCL11A indispensable à la répression des gènes gamma de globine à l'âge adulte [7] ; -délétions emportant la locus control region (LCR) : il s'agit de délétions plus ou moins larges qui emportent tout ou partie de la région qui régule la transcription de l'intégralité du cluster ␤-globine. Les délétions décrites au niveau de cette région semblent indiquer que c'est la région HS3 qui est primordiale pour la transcription du cluster ␤-globine puisque son absence est le point commun à toutes les délétions de ce type entraînant une (␥␦␤) 0 -thalassémie [8]. …”

“…En revanche, dans le cas de la délétion (␦␤) 0 -thal., le taux d'HbF est souvent compris entre 10 et 20 %, ce qui, associé à l'hypochromie et à la microcytose, suffit à faire suspecter le diagnostic de (␦␤) 0 -thalassémie. En revanche, les délétions emportant la région HS3 du LCR et qui inactivent donc tout le cluster ␤-globine du chromosome 11 touché n'ont aucune traduction sur le bilan phénotypique de l'hémoglobine [8]. …”